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Jin GN, Wang Y, Liu YM, Lu YN, Lu JM, Wang JH, Ma JW, Quan YZ, Gao HY, Cui YX, Xu X, Piao LX. Arctiin Mitigates Neuronal Injury by Modulating the P2X7R/NLPR3 Inflammasome Signaling Pathway. Inflammation 2024:10.1007/s10753-024-02117-z. [PMID: 39154088 DOI: 10.1007/s10753-024-02117-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 06/13/2024] [Accepted: 07/30/2024] [Indexed: 08/19/2024]
Abstract
Depression, recognized globally as a primary cause of disability, has its pathogenesis closely related to neuroinflammation and neuronal damage. Arctiin (ARC), the major bioactive component of Fructus arctii, has various pharmacological activities, such as anti-inflammatory and neuroprotective effects. Building on previous findings that highlighted ARC's capability to mitigate depression by dampening microglial hyperactivation and thereby reducing neuroinflammatory responses and cortical neuronal damage in mice, the current study delves deeper into ARC's therapeutic potential by examining its impact on hippocampal neuronal damage in depression. Utilizing both chronic unpredictable mild stress (CUMS)-induced depression model in mice and corticosterone (CORT)-stimulated PC12 cell model of neuronal damage, the techniques including Nissl staining, immunohistochemistry, western blotting, ELISA, lactate dehydrogenase assays, colony formation assays, immunofluorescence staining and molecular docking were employed to unravel the mechanisms behind ARC's neuroprotective effects. The findings revealed that ARC not only mitigates hippocampal neuropathological damage and reduces serum CORT levels in CUMS-exposed mice but also enhances cell activity while reducing lactate dehydrogenase release in CORT-stimulated PC12 cells. ARC attenuated neuroinflammatory responses and neuronal apoptosis by inhibiting the overactivation of the P2X7 receptor (P2X7R)/NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signaling pathway, similar to the effect of A438079 (P2X7R antagonist). Interestingly, pretreatment with A438079 blocked the neuroprotective effect of ARC. Computer modeling predicted that both ARC and A438079 have strong binding with P2X7R and they have the same binding site. These results suggested that ARC may exert a neuroprotective role by binding to P2X7R, thereby inhibiting the P2X7R/NLRP3 inflammasome signaling pathway.
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Affiliation(s)
- Guang-Nan Jin
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China
| | - Yu Wang
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China
| | - Yi-Ming Liu
- Department of Neurology, Yanbian University Hospital, Yanbian University, Yanji, 133000, Jilin Province, China
| | - Yu-Nan Lu
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China
| | - Jing-Mei Lu
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China
| | - Jing-He Wang
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China
| | - Jing-Wen Ma
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China
| | - Yan-Zhu Quan
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China
| | - Hong-Yan Gao
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China
| | - Yue-Xian Cui
- Department of Neurology, Yanbian University Hospital, Yanbian University, Yanji, 133000, Jilin Province, China.
| | - Xiang Xu
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China.
| | - Lian-Xun Piao
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China.
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Ersoy B, Herzog ML, Pan W, Schilling S, Endres M, Göttert R, Kronenberg GD, Gertz K. The atypical antidepressant tianeptine confers neuroprotection against oxygen-glucose deprivation. Eur Arch Psychiatry Clin Neurosci 2024; 274:777-791. [PMID: 37653354 PMCID: PMC11127858 DOI: 10.1007/s00406-023-01685-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Accepted: 08/14/2023] [Indexed: 09/02/2023]
Abstract
Proregenerative and neuroprotective effects of antidepressants are an important topic of inquiry in neuropsychiatric research. Oxygen-glucose deprivation (OGD) mimics key aspects of ischemic injury in vitro. Here, we studied the effects of 24-h pretreatment with serotonin (5-HT), citalopram (CIT), fluoxetine (FLU), and tianeptine (TIA) on primary mouse cortical neurons subjected to transient OGD. 5-HT (50 μM) significantly enhanced neuron viability as measured by MTT assay and reduced cell death and LDH release. CIT (10 μM) and FLU (1 μM) did not increase the effects of 5-HT and neither antidepressant conferred neuroprotection in the absence of supplemental 5-HT in serum-free cell culture medium. By contrast, pre-treatment with TIA (10 μM) resulted in robust neuroprotection, even in the absence of 5-HT. Furthermore, TIA inhibited mRNA transcription of candidate genes related to cell death and hypoxia and attenuated lipid peroxidation, a hallmark of neuronal injury. Finally, deep RNA sequencing of primary neurons subjected to OGD demonstrated that OGD induces many pathways relating to cell survival, the inflammation-immune response, synaptic dysregulation and apoptosis, and that TIA pretreatment counteracted these effects of OGD. In conclusion, this study highlights the comparative strength of the 5-HT independent neuroprotective effects of TIA and identifies the molecular pathways involved.
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Affiliation(s)
- Burcu Ersoy
- Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Center for Stroke Research Berlin, Department of Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Berlin-Brandenburg School for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Marie-Louise Herzog
- Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Center for Stroke Research Berlin, Department of Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- DZHK (German Center for Cardiovascular Research), Partner site, Berlin, Germany
| | - Wen Pan
- Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Center for Stroke Research Berlin, Department of Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- DZHK (German Center for Cardiovascular Research), Partner site, Berlin, Germany
| | - Simone Schilling
- Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Center for Stroke Research Berlin, Department of Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- DZHK (German Center for Cardiovascular Research), Partner site, Berlin, Germany
- Berlin Institute of Health at Charité, Universitätsmedizin Berlin, Berlin, Germany
| | - Matthias Endres
- Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Center for Stroke Research Berlin, Department of Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- DZHK (German Center for Cardiovascular Research), Partner site, Berlin, Germany
- Einstein Center for Neurosciences, Charité-Universitätsmedizin Berlin, Berlin, Germany
- DZNE (German Center for Neurodegenerative Diseases), Partner site, Berlin, Germany
- DZPG (German Center for Mental Health), Partner site, Berlin, Germany
| | - Ria Göttert
- Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Center for Stroke Research Berlin, Department of Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- DZHK (German Center for Cardiovascular Research), Partner site, Berlin, Germany
| | - Golo D Kronenberg
- Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zürich, Lenggstrasse 31, P.O. Box 363, 8032, Zurich, Switzerland
| | - Karen Gertz
- Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
- Center for Stroke Research Berlin, Department of Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
- DZHK (German Center for Cardiovascular Research), Partner site, Berlin, Germany.
- Einstein Center for Neurosciences, Charité-Universitätsmedizin Berlin, Berlin, Germany.
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Wang C, Gao MQ. Research Progress on the Antidepressant Effects of Baicalin and Its Aglycone Baicalein: A Systematic Review of the Biological Mechanisms. Neurochem Res 2024; 49:14-28. [PMID: 37715823 DOI: 10.1007/s11064-023-04026-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Revised: 08/16/2023] [Accepted: 08/31/2023] [Indexed: 09/18/2023]
Abstract
Depression is the most prevalent mental disorder, affecting more than 300 million adults worldwide each year, which can lead to serious economic and social problems. Antidepressants are usually the first-line treatment for depression, however, traditional antidepressants on the market have the disadvantage of low remission rates and may cause side effects to patients, therefore, the current focus in the field of depression is to develop novel therapeutic agents with high remission rates and few side effects. In this context, the antidepressant effects of natural compounds have received attention. Baicalin (baicalein-7-O-glucuronide) and its aglycone baicalein (5,6,7-trihydroxyflavone) are flavonoid compounds extracted from the root of Scutellaria baicalensis. Although lacking the support of clinical data, they have been shown to have significantly promising antidepressant activity in many preclinical studies through various rodent models of depression. This paper reviews the antidepressant effects of baicalin and baicalein in experimental animal models, with emphasis on summarizing the molecular mechanisms of their antidepressant effects including regulation of the HPA axis, inhibition of inflammation and oxidative stress, reduction of neuronal apoptosis and promotion of neurogenesis, as well as amelioration of mitochondrial dysfunction. Controlled clinical trials should be conducted in the future to examine the effects of baicalin and baicalein on depression in humans.
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Affiliation(s)
- Chen Wang
- Department of Clinical Pharmacology, School of Pharmacy, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning, China
| | - Ming-Qi Gao
- Department of Clinical Pharmacology, School of Pharmacy, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning, China.
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Jung K, Kwon JT. Tianeptine Affects the Improvement of Behavioral Defects, such as Schizophrenia, Caused by Maternal Immune Activation in the Mice Offspring. Cent Nerv Syst Agents Med Chem 2023; 23:CNSAMC-EPUB-134286. [PMID: 37670703 PMCID: PMC10680080 DOI: 10.2174/1871524923666230905142700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 07/10/2023] [Accepted: 07/19/2023] [Indexed: 09/07/2023]
Abstract
BACKGROUND Simultaneously with studies on animal models of fetal-induced maternal immune activation, related studies documented behavior, neurophysiological, and/or neurochemical disorders observed in some neuropsychiatric disorders, including autism and schizophrenia. OBJECTIVE To investigate whether treatment tianeptine might ameliorate maternal immune activation (MIA)-induced behavioral deficits in the offspring. MATERIALS AND METHODS The pregnant mice were injected through tail vein injection at a concentration of 5 mg/kg of polyriboinosinic-polyribocytidilic acid (polyI:C) and/or used saline as a vehicle. The injection was performed on the 9th day of pregnancy. Each group of MIA offspring was subjected to vehicle, clozapine, or tianeptine treatment. RESULTS In prepulse inhibition (PPI) test, oral treatment with tianeptine ameliorated MIA-induced sensorimotor gating deficit. Most behavioral parameters of social interaction test (SIT), forced swimming test (FST), and open field test (OFT) were significantly changed in the MIA offspring. Tianeptine treatment significantly recovered behavioral changes observed in the SIT, OFT, and FST. In order to confirm expression level of neurodevelopmental proteins, immunohistochemical image analysis and Western blot were performed, and the medial prefrontal cortex (mPFC) was targeted. As a result, it was confirmed that the neurodevelopmental proteins were decreased, which was recovered after administration of tianeptine to MIA offspring. CONCLUSION Tianeptine might be useful for treating psychiatric disorders with neurodevelopmental issues.
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Affiliation(s)
- Kooseung Jung
- Department of Clinical Pharmacology, College of Medicine, Soon Chun Hyang University, Cheonan, Republic of Korea
| | - Jun-Tack Kwon
- Department of Clinical Pharmacology, College of Medicine, Soon Chun Hyang University, Cheonan, Republic of Korea
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Jiang S, Yang H, Li M. Emerging Roles of Lysophosphatidic Acid in Macrophages and Inflammatory Diseases. Int J Mol Sci 2023; 24:12524. [PMID: 37569902 PMCID: PMC10419859 DOI: 10.3390/ijms241512524] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 08/02/2023] [Accepted: 08/04/2023] [Indexed: 08/13/2023] Open
Abstract
Lysophosphatidic acid (LPA) is a bioactive phospholipid that regulates physiological and pathological processes in numerous cell biological functions, including cell migration, apoptosis, and proliferation. Macrophages are found in most human tissues and have multiple physiological and pathological functions. There is growing evidence that LPA signaling plays a significant role in the physiological function of macrophages and accelerates the development of diseases caused by macrophage dysfunction and inflammation, such as inflammation-related diseases, cancer, atherosclerosis, and fibrosis. In this review, we summarize the roles of LPA in macrophages, analyze numerous macrophage- and inflammation-associated diseases triggered by LPA, and discuss LPA-targeting therapeutic strategies.
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Affiliation(s)
- Shufan Jiang
- Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200080, China;
- Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Huili Yang
- Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200080, China;
| | - Mingqing Li
- Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200080, China;
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200080, China
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Ma Z, Feng D, Rui W, Wang Z. Baicalin attenuates chronic unpredictable mild stress-induced hippocampal neuronal apoptosis through regulating SIRT1/PARP1 signaling pathway. Behav Brain Res 2023; 441:114299. [PMID: 36642102 DOI: 10.1016/j.bbr.2023.114299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 12/29/2022] [Accepted: 01/11/2023] [Indexed: 01/13/2023]
Abstract
Baicalin (BA), a flavonoid glycoside extracts from Scutellaria baicalensis Georgi, has been reported to exert antidepressant effects. Emerging evidence indicates that neuronal apoptosis plays a crucial role in the pathogenesis of depression. Poly (ADP-ribose) polymerase-1 (PARP1) is established as a key regulator of the cellular apoptosis. In the present study, we explored whether BA exerts antidepressant effects by regulating PARP1 signaling pathway and elucidated the underlying mechanisms. We found that administration of BA (30 mg/kg, 60 mg/kg) alleviated chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors by increasing sucrose consumption in sucrose preference test (SPT), improving activity status in open field test (OFT) and reducing rest time in tail suspension test (TST). Hematoxylin and eosin (HE) staining and Nissl staining showed that BA ameliorated CUMS-induced neuronal damage in the hippocampus. Moreover, BA significantly upregulated anti-apoptotic protein Bcl-2, downregulated pro-apoptotic protein Bax and cleaved-caspase-3 after CUMS in hippocampal of mice. Intriguingly, western blot and immunohistochemistry (IHC) results showed that the protein level of PARP1 was significantly increased in hippocampal tissue after CUMS, which was reversed by BA treatment. In primary hippocampal neurons (PHNs), BA abrogated the neuronal apoptosis caused by PARP1 overexpression. Meanwhile, BA significantly increased the protein level of SIRT1, SIRT1 inhibitor (EX-527) treatment reversed the effect of BA on reducing the protein level of PARP1 and neuronal apoptosis in CUMS-induced mice. Overall, our results indicated that BA attenuated the CUMS-induced hippocampal neuronal apoptosis through regulating the SIRT1/PARP1 signaling pathway.
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Affiliation(s)
- Zhongxuan Ma
- Department of Pharmacy, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210029, Jiangsu, China.
| | - Dingding Feng
- Department of Pharmaceutical Sciences, Jiangsu Health Vocational College, Nanjing 211800, Jiangsu, China
| | - Wenjuan Rui
- Department of Clinical Laboratory, Shanghai East Hospital, Tongji University School of Medicine, 150 Ji Mo Road, Shanghai 200120, China
| | - Zhiqing Wang
- Department of Pharmacy, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210029, Jiangsu, China.
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Male Stressed Mice Having Behavioral Control Exhibit Escalations in Dorsal Dentate Adult-Born Neurons and Spatial Memory. Int J Mol Sci 2023; 24:ijms24031983. [PMID: 36768303 PMCID: PMC9916676 DOI: 10.3390/ijms24031983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/13/2023] [Accepted: 01/16/2023] [Indexed: 01/21/2023] Open
Abstract
An escapable (ES)/inescapable stress (IS) paradigm was used to study whether behavioral control and repeated footshock stressors may affect adult neurogenesis and related cognitive function. Male stressed mice having behavioral control (ES) had a short-term escalation in dorsal dentate gyrus (DG) neurogenesis, while similarly stressed mice having no such control had unaltered neurogenesis as compared to control mice receiving no stressors. Paradoxically, ES and IS mice had comparable stress-induced corticosterone elevations throughout the stress regimen. Appetitive operant conditioning and forced running procedures were used to model learning and exercise effects in this escapable/inescapable paradigm. Further, conditioning and running procedures did not seem to affect the mice's corticosterone or short-term neurogenesis. ES and IS mice did not show noticeable long-term changes in their dorsal DG neurogenesis, gliogenesis, local neuronal density, apoptosis, autophagic flux, or heterotypic stress responses. ES mice were found to have a greater number of previously labeled and functionally integrated DG neurons as compared to IS and control mice 6 weeks after the conclusion of the stressor regimen. Likewise, ES mice outperformed IS and non-stressed control mice for the first two, but not the remaining two, trials in the object location task. Compared to non-stressed controls, temozolomide-treated ES and IS mice having a lower number of dorsal DG 6-week-old neurons display poor performance in their object location working memory. These results, taken together, prompt us to conclude that repeated stressors, albeit their corticosterone secretion-stimulating effect, do not necessary affect adult dorsal DG neurogenesis. Moreover, stressed animals having behavioral control may display adult neurogenesis escalation in the dorsal DG. Furthermore, the number of 6-week-old and functionally-integrated neurons in the dorsal DG seems to confer the quality of spatial location working memory. Finally, these 6-week-old, adult-born neurons seem to contribute spatial location memory in a use-dependent manner.
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Li T, Li X, Zhang J, Yu Z, Gong F, Wang J, Tang H, Xiang J, Zhang W, Cai D. Chemical component analysis of the traditional Chinese medicine Guipi Tang and its effects on major depressive disorder at molecular level. Heliyon 2022; 8:e12182. [DOI: 10.1016/j.heliyon.2022.e12182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 11/21/2022] [Accepted: 11/30/2022] [Indexed: 12/14/2022] Open
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Xu H, Ding Y, Qi X, Zhang ZJ, Su J. Ameliorated Neurogenesis Deficits in Dentate Gyrus May Underly the Pronounced Antidepressant Effect of TREK-1 Potassium Channel Blockade in Rats with Depressive-like Behavior. ACS Chem Neurosci 2022; 13:3068-3077. [PMID: 36269040 DOI: 10.1021/acschemneuro.2c00428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Depression is considered to be the most common mental disorder and is probed by several studies that chronic mild stress contributes to depression, and fortunately, most antidepressants ameliorate depressive-like behavior accompanied with reversed hippocampal neurogenesis defects. In our present study, we confirmed that different antidepressants repaired the stress-induced neuronal and behavioral deficits by modulating adult hippocampal neurogenesis. Antidepressant treatment restored the adult hippocampal neurodegeneration, which was impaired by chronic unpredicted mild stress displaying decreased proliferation and neuronal differentiation but increased apoptosis of newly formed neurons in dentate gyrus. Notably, sucrose preference ratio significantly correlated with both neuronal differentiation proportion and newborn apoptosis proportion, suggesting a mechanistic relationship between neurogenesis and behavior. Indeed, the neotype TREK-1 potassium channel blocker expressed an earlier and pronounced antidepressant manifestation compared to the traditional selective serotonin-reuptake inhibitors fluoxetine. We therefore conclude that the administration of TREK-1 potassium channel antagonism can reverse the depressive deficits caused by chronic stress quickly via regulation of adult hippocampal neurogenesis.
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Affiliation(s)
- Hua Xu
- Department of Neurology, Affiliated Jintan Hospital of Jiangsu University, Changzhou Jintan First People's Hospital, Changzhou, Jiangsu 213200, China.,Department of Neurology, First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China
| | - Yingpeng Ding
- Department of Cardiology, Affiliated Jintan Hospital of Jiangsu University, Changzhou Jintan First People's Hospital, Changzhou 213200, Jiangsu, China
| | - Xinyang Qi
- Department of Neurology, Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China
| | - Zhi-Jun Zhang
- Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China.,The Brain Cognition and Brain Disease Institute (BCBDI), CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen Institute of Advanced Technology, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China
| | - Jianhua Su
- Department of Neurology, Affiliated Jintan Hospital of Jiangsu University, Changzhou Jintan First People's Hospital, Changzhou, Jiangsu 213200, China
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Bai Y, Dai G, Song L, Gu X, Ba N, Ju W, Zhang W. Potential Anti-Depressive Effects and Mechanisms of Zhi-Zi Hou-Po Decoction Using Behavioral Despair Tests Combined With in Vitro Approaches. Front Pharmacol 2022; 13:918776. [PMID: 35873590 PMCID: PMC9298739 DOI: 10.3389/fphar.2022.918776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 06/15/2022] [Indexed: 11/13/2022] Open
Abstract
Zhi-Zi Hou-Po Decoction (ZHD) has been widely used in the treatment of depression for centuries. This study aimed to investigate the antidepressant effects of the water extract of ZHD (ZHD-WE) and ethanol extract of ZHD (ZHD-EE) using behavioral despair tests in mice, and to further explore the neuroprotective effects in a PC12 cell injury model induced by corticosterone (CORT). Mice were divided into a control group (normal saline), ZHD-WE groups (4, 8, and 16 g kg-1), ZHD-EE groups (4, 8, and 16 g kg-1) and the fluoxetine group (20 mg kg-1). The forced swimming test (FST) and tail suspension test (TST) were used to screen the antidepressant effects of ZHD-WE and ZHD-EE after oral administration for seven consecutive days. The level of brain-derived neurotrophic factor (BDNF) in the hippocampus was determined by ELISA. The MTT, lactate dehydrogenase (LDH) and flow cytometry analysis were performed to elucidate the neuroprotective effect of ZHD-EE on a PC12 cell injury model. Additionally, the mRNA and proteins expression of apoptotic molecules Bax, Bcl-2 and BDNF were detected by RT-PCR and western blot assay. It showed that ZHD-EE at concentrations of 8 and 16 g kg-1 significantly decreased the immobility time in the TST and FST, and increased the BDNF levels in the hippocampus. While ZHD-WE at concentrations of 4, 8, and 16 g kg-1 had no significant effect on the immobility time in the TST, and only the 16 g kg-1 of extract group significantly decreased the immobility time in the FST. In vitro, the obtained results showed that PC12 cells pre-incubated with ZHD-EE at concentrations of 100 and 400 μg ml-1 improved cell viability, decreased LDH release, and reduced apoptosis rate of PC12 cells. Moreover, ZHD-EE significantly increased the mRNA and proteins expression of Bcl-2 and BDNF, while decreased the mRNA and protein expression of Bax. ZHD-EE significantly improved despair-like behavior in mice, and its mechanism may be related to BDNF upregulation in the hippocampus. This study also showed that ZHD-EE had a protective effect on CORT-induced injury in PC12 cells by upregulating the expression of BDNF and restoring Bcl-2/Bax balance.
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Affiliation(s)
- Yongtao Bai
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.,Clinical Research Center, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Guoliang Dai
- Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Lihua Song
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Xiaolei Gu
- Clinical Research Center, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Ning Ba
- Clinical Research Center, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Wenzheng Ju
- Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Wenzhou Zhang
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
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11
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Perić I, Costina V, Djordjević S, Gass P, Findeisen P, Inta D, Borgwardt S, Filipović D. Tianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats. Sci Rep 2021; 11:17747. [PMID: 34493757 PMCID: PMC8423821 DOI: 10.1038/s41598-021-97186-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 08/09/2021] [Indexed: 11/09/2022] Open
Abstract
Deregulation of synaptic function and neurotransmission has been linked with the development of major depression disorder (MDD). Tianeptine (Tian) has been used as antidepressant with anxiolytic properties and recently as a nootropic to improve cognitive performance, but its mechanism of action is unknown. We conducted a proteomic study on the hippocampal synaptosomal fractions of adult male Wistar rats exposed to chronic social isolation (CSIS, 6 weeks), an animal model of depression and after chronic Tian treatment in controls (nootropic effect) and CSIS-exposed rats (lasting 3 weeks of 6-week CSIS) (therapeutic effect). Increased expression of Syn1 and Camk2-related neurotransmission, vesicle transport and energy processes in Tian-treated controls were found. CSIS led to upregulation of proteins associated with actin cytoskeleton, signaling transduction and glucose metabolism. In CSIS rats, Tian up-regulated proteins involved in mitochondrial energy production, mitochondrial transport and dynamics, antioxidative defense and glutamate clearance, while attenuating the CSIS-increased glycolytic pathway and cytoskeleton organization proteins expression and decreased the expression of proteins involved in V-ATPase and vesicle endocytosis. Our overall findings revealed that synaptic vesicle dynamics, specifically exocytosis, and mitochondria-related energy processes might be key biological pathways modulated by the effective nootropic and antidepressant treatment with Tian and be a potential target for therapeutic efficacy of the stress-related mood disorders.
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Affiliation(s)
- Ivana Perić
- Department of Molecular Biology and Endocrinology, "VINČA", Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Victor Costina
- Institute for Clinical Chemistry, Medical Faculty Mannheim of the University of Heidelberg, University Hospital Mannheim, 68159, Mannheim, Germany
| | | | - Peter Gass
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159, Mannheim, Germany
| | - Peter Findeisen
- Institute for Clinical Chemistry, Medical Faculty Mannheim of the University of Heidelberg, University Hospital Mannheim, 68159, Mannheim, Germany
| | - Dragoš Inta
- Department of Psychiatry (UPK), University of Basel, Basel, Switzerland
| | - Stefan Borgwardt
- Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany
| | - Dragana Filipović
- Department of Molecular Biology and Endocrinology, "VINČA", Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia.
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12
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Life and Death of Immature Neurons in the Juvenile and Adult Primate Amygdala. Int J Mol Sci 2021; 22:ijms22136691. [PMID: 34206571 PMCID: PMC8268704 DOI: 10.3390/ijms22136691] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 06/11/2021] [Accepted: 06/18/2021] [Indexed: 12/12/2022] Open
Abstract
In recent years, a large population of immature neurons has been documented in the paralaminar nucleus of the primate amygdala. A substantial fraction of these immature neurons differentiate into mature neurons during postnatal development or following selective lesion of the hippocampus. Notwithstanding a growing number of studies on the origin and fate of these immature neurons, fundamental questions about the life and death of these neurons remain. Here, we briefly summarize what is currently known about the immature neurons present in the primate ventral amygdala during development and in adulthood, as well as following selective hippocampal lesions. We provide evidence confirming that the distribution of immature neurons extends to the anterior portions of the entorhinal cortex and layer II of the perirhinal cortex. We also provide novel arguments derived from stereological estimates of the number of mature and immature neurons, which support the view that the migration of immature neurons from the lateral ventricle accompanies neuronal maturation in the primate amygdala at all ages. Finally, we propose and discuss the hypothesis that increased migration and maturation of neurons in the amygdala following hippocampal dysfunction may be linked to behavioral alterations associated with certain neurodevelopmental disorders.
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13
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Ortiz JB, Newbern J, Conrad CD. Chronic stress has different immediate and delayed effects on hippocampal calretinin- and somatostatin-positive cells. Hippocampus 2021; 31:221-231. [PMID: 33241879 DOI: 10.1002/hipo.23285] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 10/13/2020] [Accepted: 11/15/2020] [Indexed: 12/22/2022]
Abstract
Past studies find that chronic stress alters inhibitory, GABAergic circuitry of neurons in distinct hippocampal subregions. Less clear is whether these effects persist weeks after chronic stress ends, and whether these effects involve changes in the total number of hippocampal GABAergic neurons or modulates the function of specific GABAergic subtypes. A transgenic mouse line (VGAT:Cre Ai9) containing an indelible marker for GABAergic neurons (tdTomato) throughout the brain was used to determine whether chronic stress alters total GABAergic neuronal number or the expression of two key GABAergic cell subtypes, calretinin expressing (CR+) and somatostatin expressing (SOM+) neurons, and whether these changes endure weeks later. Male and female mice were chronically stressed in wire mesh restrainers for 6h/d/21d (Str) or not (Con), and then allowed a 3 week rest period (Str-Rest) and compared to those without a rest period (Str-NoRest). Epifluorescent microscope images of immunohistochemistry-processed brains were quantified to estimate the total number of fluorescently-labeled hippocampal GABAergic neurons and the proportion that were CR+ or SOM+. Neither chronic stress nor sex altered the total number of GABAergic cells. In contrast, chronic stress reduced the expression of CR+ in the CA3 region of the hippocampus in both males and females, with robust reductions in the DG region of males, but not females, and these changes reversed following a rest period. Chronic stress also reduced the proportion of hippocampal SOM+ neurons and this reduction persisted even with a rest period. These results show chronic stress dynamically reduced CR expression without changing total inhibitory neuronal number and point to CR as a potential new lead to understand mechanisms by which chronic stress alters hippocampal function.
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Affiliation(s)
- J Bryce Ortiz
- Department of Psychology, Arizona State University, Tempe, Arizona, USA
| | - Jason Newbern
- School of Life Sciences, Arizona State University, Tempe, Arizona, USA
| | - Cheryl D Conrad
- Department of Psychology, Arizona State University, Tempe, Arizona, USA
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14
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Lin CH, Chiu HE, Wu SY, Tseng ST, Wu TC, Hung YC, Hsu CY, Chen HJ, Hsu SF, Kuo CE, Hu WL. Chinese Herbal Products for Non-Motor Symptoms of Parkinson's Disease in Taiwan: A Population-Based Study. Front Pharmacol 2021; 11:615657. [PMID: 33584294 PMCID: PMC7873047 DOI: 10.3389/fphar.2020.615657] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 12/23/2020] [Indexed: 11/20/2022] Open
Abstract
Objective: Combinations of Chinese herbal products (CHPs) are widely used for Parkinson’s disease (PD) in Taiwan. Thereby, we investigated the use of CHPs in patients with PD. Methods: This study was a population-based cohort study that analyzed the data of patients with PD from the National Health Insurance Research Database. A total of 9,117 patients were selected from a random sample of one million individuals included in this database. We used multiple logistic regression models to estimate the adjusted odds ratios of the demographic factors and analyzed the formula and single CHPs commonly used for PD. Results: Traditional Chinese medicine users were more commonly female, younger, of white-collar status, and residents of Central Taiwan. Chaihu-Jia-Longgu-Muli-Tang was the most commonly used formula, followed by Ma-Zi-Ren-Wan and then Shao-Yao-Gan-Cao-Tang. The most commonly used single herb was Uncaria tomentosa (Willd. ex Schult.) DC., followed by Gastrodia elata Blume and then Radix et Rhizoma Rhei (Rheum palmatum L., Rheum tanguticum Maxim. ex Balf., and Rheum officinale Baill.). Chaihu-Jia-Longgu-Muli-Tang and U. tomentosa (Willd. ex Schult.) DC. have shown neuroprotective effects in previous studies, and they have been used for managing non-motor symptoms of PD. Conclusion: Chaihu-Jia-Longgu-Muli-Tang and U. tomentosa (Willd. ex Schult.) DC. are the most commonly used CHPs for PD in Taiwan. Our results revealed the preferences in medication prescriptions for PD. Further studies are warranted to determine the effectiveness of these CHPs for ameliorating the various symptoms of PD, their adverse effects, and the mechanisms underlying their associated neuroprotective effects.
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Affiliation(s)
- Chien-Hung Lin
- Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hsienhsueh Elley Chiu
- Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Szu-Ying Wu
- Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.,Department of Nursing, Meiho University, Pingtung, Taiwan.,Department of Sports Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shih-Ting Tseng
- Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tzu-Chan Wu
- Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yu-Chiang Hung
- Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.,School of Chinese Medicine for Post Baccalaureate, I-Shou University, Kaohsiung, Taiwan
| | - Chung Y Hsu
- Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
| | - Hsuan-Ju Chen
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan.,College of Medicine, China Medical University, Taichung, Taiwan
| | - Sheng-Feng Hsu
- Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan.,Department of Chinese Medicine, China Medical University Hospital, Taipei, Taiwan
| | - Chun-En Kuo
- Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.,Department of Nursing, Meiho University, Pingtung, Taiwan
| | - Wen-Long Hu
- Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.,Kaohsiung Medical University College of Medicine, Kaohsiung, Taiwan.,Fooyin University College of Nursing, Kaohsiung, Taiwan
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15
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Changes in Hippocampal Plasticity in Depression and Therapeutic Approaches Influencing These Changes. Neural Plast 2020; 2020:8861903. [PMID: 33293948 PMCID: PMC7718046 DOI: 10.1155/2020/8861903] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 09/30/2020] [Accepted: 11/11/2020] [Indexed: 02/06/2023] Open
Abstract
Depression is a common neurological disease that seriously affects human health. There are many hypotheses about the pathogenesis of depression, and the most widely recognized and applied is the monoamine hypothesis. However, no hypothesis can fully explain the pathogenesis of depression. At present, the brain-derived neurotrophic factor (BDNF) and neurogenesis hypotheses have highlighted the important role of plasticity in depression. The plasticity of neurons and glial cells plays a vital role in the transmission and integration of signals in the central nervous system. Plasticity is the adaptive change in the nervous system in response to changes in external signals. The hippocampus is an important anatomical area associated with depression. Studies have shown that some antidepressants can treat depression by changing the plasticity of the hippocampus. Furthermore, caloric restriction has also been shown to affect antidepressant and hippocampal plasticity changes. In this review, we summarize the latest research, focusing on changes in the plasticity of hippocampal neurons and glial cells in depression and the role of BDNF in the changes in hippocampal plasticity in depression, as well as caloric restriction and mitochondrial plasticity. This review may contribute to the development of antidepressant drugs and elucidating the mechanism of depression.
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16
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Ghasemzadeh Rahbardar M, Hosseinzadeh H. Effects of rosmarinic acid on nervous system disorders: an updated review. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2020; 393:1779-1795. [PMID: 32725282 DOI: 10.1007/s00210-020-01935-w] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 06/29/2020] [Indexed: 02/07/2023]
Abstract
Nowadays, the worldwide interest is growing to use medicinal plants and their active constituents to develop new potent medicines with fewer side effects. Precise dietary compounds have prospective beneficial applications for various neurodegenerative ailments. Rosmarinic acid is a polyphenol and is detectable most primarily in many Lamiaceae families, for instance, Rosmarinus officinalis also called rosemary. This review prepared a broad and updated literature review on rosmarinic acid elucidating its biological activities on some nervous system disorders. Rosmarinic acid has significant antinociceptive, neuroprotective, and neuroregenerative effects. In this regard, we classified and discussed our findings in different nervous system disorders including Alzheimer's disease, epilepsy, depression, Huntington's disease, familial amyotrophic lateral sclerosis, Parkinson's disease, cerebral ischemia/reperfusion injury, spinal cord injury, stress, anxiety, and pain.
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Affiliation(s)
| | - Hossein Hosseinzadeh
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
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17
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Modulation of LPA1 receptor-mediated neuronal apoptosis by Saikosaponin-d: A target involved in depression. Neuropharmacology 2019; 155:150-161. [DOI: 10.1016/j.neuropharm.2019.05.027] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Revised: 05/13/2019] [Accepted: 05/20/2019] [Indexed: 12/13/2022]
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18
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Alamo C, García-Garcia P, Lopez-Muñoz F, Zaragozá C. Tianeptine, an atypical pharmacological approach to depression. REVISTA DE PSIQUIATRIA Y SALUD MENTAL 2019; 12:170-186. [PMID: 30612921 DOI: 10.1016/j.rpsm.2018.09.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 09/11/2018] [Accepted: 09/24/2018] [Indexed: 02/06/2023]
Abstract
The introduction of the first antidepressants in the 50s of the 20th century radically changed the treatment of depression, while providing information on pathophysiological aspects of this disease. New antidepressants drugs (agomelatine, tianeptine, vortioxetine) are providing data that give rise to pathophysiological hypotheses of depression that differ from the classic monoaminergic theory. In this sense, tianeptina, an atypical drug by its mechanism of differential action, contributes to clarify that in depression there is more than monoamines. Thus, tianeptine does not modify the rate of extracellular serotonin, so it does not increase or decrease the reuptake of serotonin. Chronic administration of tianeptine does not alter the density or affinity of more than a hundred classical receptors related to depression. Recently, a weak action of tianeptine on Mu opioid receptors has been described that could explain the release of dopamine in the limbic system and its participation in the modulation of glutamatergic mechanisms. These mechanisms support the hypothesis of the possible mechanism of action of this antidepressant. Tianeptine is an antidepressant, with anxiolytic properties, that can improve somatic symptoms. Tianeptine as a glutamatergic modulator, among other mechanisms, allows us to approach depression from a different point of view than other antidepressants.
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Affiliation(s)
- Cecilio Alamo
- Departamento de Ciencias Biomédicas, Facultad de Medicina y Ciencias de la Salud, Universidad de Alcalá, Alcalá de Henares, Madrid, España.
| | - Pilar García-Garcia
- Departamento de Ciencias Biomédicas, Facultad de Medicina y Ciencias de la Salud, Universidad de Alcalá, Alcalá de Henares, Madrid, España
| | - Francisco Lopez-Muñoz
- Facultad de Ciencias de la Salud, Universidad Camilo José Cela, Villanueva de la Cañada, Madrid, España; Unidad de Neuropsicofarmacología, Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, España
| | - Cristina Zaragozá
- Departamento de Ciencias Biomédicas, Facultad de Medicina y Ciencias de la Salud, Universidad de Alcalá, Alcalá de Henares, Madrid, España
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19
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Trujillo V, Durando PE, Suárez MM. Maternal separation induces long-term changes in mineralocorticoid receptor in rats subjected to chronic stress and treated with tianeptine. Int J Neurosci 2018; 129:540-550. [PMID: 30485752 DOI: 10.1080/00207454.2018.1550398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
PURPOSE The aim of this study was to analyze whether early maternal separation would result in long-term, persistent alterations in stress response in adulthood, altering mineralocorticoid receptor immunoreactivity (MR-ir) in the dorsal hippocampal areas [CA1, CA2, CA3 and dentate gyrus (DG)], paraventricular nucleus of the hypothalamus and medial and central nucleus of the amygdala, key structures involved in stress response regulation. We also analyzed whether chronic treatment with the antidepressant tianeptine reverses these possible changes. MATERIAL AND METHODS Male Wistar rats were subjected to daily maternal separation for 4.5 h during 3 weeks or left undisturbed. As adults, they were exposed to chronic stress during 24 days or left undisturbed, and they were also daily treated with tianeptine (10 mg/kg i.p.) or isotonic solution. RESULTS In the CA2 and DG areas of the dorsal hippocampus, there was an increase in MR-ir in non-maternally separated and chronic stressed groups. Tianeptine raised MR-ir in the CA3. In the DG, control and maternally separated + chronic stress groups treated with tianeptine showed more MR-ir than their respective vehicle groups. In the paraventricular nucleus, tianeptine decreased MR-ir in non-separated groups, but not in maternally separated rats. CONCLUSIONS Our results support findings that early-life events induce long-term changes in stress response regulation, persistent into adulthood, which are manifested during challenges in later life, and that treatment with tianeptine, which tends to attenuate the hypothalamus-pituitary-adrenal axis dysregulation, depends on the individual experience of each rat.
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Affiliation(s)
- Verónica Trujillo
- a Facultad de Ciencias Exactas, Físicas y Naturales , Universidad Nacional de Córdoba, Laboratorio de Fisiología Animal , Córdoba , Argentina
| | - Patricia Evelina Durando
- a Facultad de Ciencias Exactas, Físicas y Naturales , Universidad Nacional de Córdoba, Laboratorio de Fisiología Animal , Córdoba , Argentina
| | - Marta Magdalena Suárez
- a Facultad de Ciencias Exactas, Físicas y Naturales , Universidad Nacional de Córdoba, Laboratorio de Fisiología Animal , Córdoba , Argentina.,b Facultad de Ciencias Médicas , Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Universidad Nacional de Córdoba Ciudad Universitaria , Córdoba , Argentina
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20
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Ayuob NN, Balgoon MJ. Histological and molecular techniques utilized to investigate animal models of depression. An updated review. Microsc Res Tech 2018; 81:1143-1153. [PMID: 30168883 DOI: 10.1002/jemt.23105] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Revised: 06/25/2018] [Accepted: 07/16/2018] [Indexed: 12/30/2022]
Abstract
This review aimed to summarize the different histopathological techniques and procedures utilized during investigating the different animal models of depression in order to explore the pathophysiological aspect of depression and testing the efficacy of the antidepressant drugs or new treatments. This will be helpful while designing researches aiming to achieve these objectives. It was found that the major obstacle during investigating the animal models of depression was the restricted availability of validated animal models. The chronic stress models have face, construct, and predictive validity. It was found that the histological techniques used in investigating the animal models of depression that was described in the literatures fall under three categories; the light microscopic, the electron microscopic and the molecular biological studies. The light microscope studies were performed using the routine histological staining and immunohistochemical technique that aimed to describe the hippocampal histopathological changes induced by depression. Establishment of a preclinical behavioral science laboratory is highly recommended. It will encourage and support the conduction of high quality, multidisciplinary researches targeting anxiety and other psychiatric disorders and will indirectly improve the health care provided to the psychiatric patients. RESEARCH HIGHLIGHTS: Chronic stress models are valid ones. Light microscope was utilized to examine the routinely or immunohistochemically stained sections in hippocampus of animal models of depression while electron microscope was utilized to examine its ultrastructure.
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Affiliation(s)
- Nasra Naeim Ayuob
- Department of Anatomy, Faculty of Medicine, King Abdulaziz University, Saudi Arabia.,Histology Department, Faculty of Medicine, Mansoura University, Egypt
| | - Maha Jameal Balgoon
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Saudi Arabia
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21
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Halaris A. Neuroinflammation and neurotoxicity contribute to neuroprogression in neurological and psychiatric disorders. FUTURE NEUROLOGY 2018. [DOI: 10.2217/fnl-2017-0039] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
The immune system and inflammatory processes contribute to brain-related pathologies in most, if not all, neurological and psychiatric disorders. Stress is a key factor in inducing immune system dysregulation in conjunction with genetic, epigenetic and environmental factors. Activation of the immune response can alter neurotransmission leading, among others, to serotonin deficiency, and increased production of neurotoxic substances contributing to disease progression. The concept of neuroprogression is gaining acceptance among clinicians and researches as it seeks to explain the mechanism(s) responsible for disease chronicity, recurrence and treatment resistance. Therefore, measurement of neuroinflammatory biomarkers along with assessment of neurotoxic metabolites, oxidative stress and neuroplasticity impairment, will ultimately be useful tools to predict and possibly prevent the development and progression of neuropsychiatric disorders as well as to identify the most efficacious treatments.
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Affiliation(s)
- Angelos Halaris
- Department of Psychiatry & Behavioral Neuroscience, Loyola University Stritch School of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA
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22
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Khalili-Fomeshi M, Azizi MG, Esmaeili MR, Gol M, Kazemi S, Ashrafpour M, Moghadamnia AA, Hosseinzadeh S. Piperine restores streptozotocin-induced cognitive impairments: Insights into oxidative balance in cerebrospinal fluid and hippocampus. Behav Brain Res 2018; 337:131-138. [DOI: 10.1016/j.bbr.2017.09.031] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2017] [Revised: 09/05/2017] [Accepted: 09/18/2017] [Indexed: 02/02/2023]
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23
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Liu S, Han S, Dai Q, Li S, Li J. BICAO-induced ischaemia caused depressive-like behaviours and caspase-8/-9-dependent brain regional neural cell apoptosis in mice. Stroke Vasc Neurol 2017; 3:1-8. [PMID: 29600001 PMCID: PMC5870644 DOI: 10.1136/svn-2017-000109] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Revised: 11/04/2017] [Accepted: 11/07/2017] [Indexed: 11/04/2022] Open
Abstract
Introduction Cerebral ischaemia-induced depression is among the most frequent neuropsychiatric consequences and adversely impact the prognosis and recovery of patients. Although several brain regions have been implied in the development of ischaemia-induced depression, the brain region-specific neural cell apoptosis pathways have not been clarified yet. Methods In this study, bilateral internal carotid artery occlusion (BICAO) mouse model was established to induce cerebral ischaemia. Sucrose preference, tail suspension and forced swim tests were conducted on mice at 7, 21 and 30 days after BICAO treatment. In addition, brain regional ischaemic neuron loss was investigated by using immunofluorescent staining of neuronal nuclei (NeuN) and caspase-8/-9-dependent cell apoptosis was also examined by western blot analysis. Results BICAO-induced cerebral ischaemia resulted in decreased sucrose preference and increased immobility times, which were representative depressive-like behaviours of mice until 30 days after BICAO treatment compared with Sham-operated mice. This outcome was associated with significant neuron loss by using immunofluorescent staining and increased cleavage levels of pro-caspase-3/-8/-9, but not pro-caspase-12, by western blot analysis in hypothalamus, midbrain, prefrontal cortex and hippocampus of mice. Conclusions This study showed that BICAO-induced ischaemia caused depressive-like behaviours and caspase-8/-9-dependent neural cell apoptosis in several brain regions, including hypothalamus and midbrain of mice.
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Affiliation(s)
- Shuiqiao Liu
- Department of Neurobiology and Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China
| | - Song Han
- Department of Neurobiology and Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China
| | - Qingqing Dai
- Department of Neurobiology and Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China
| | - Shujuan Li
- Department of Neurology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Junfa Li
- Department of Neurobiology and Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China
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24
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Can Ocimum basilicum relieve chronic unpredictable mild stress-induced depression in mice? Exp Mol Pathol 2017; 103:153-161. [DOI: 10.1016/j.yexmp.2017.08.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Revised: 08/12/2017] [Accepted: 08/16/2017] [Indexed: 12/31/2022]
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25
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Park G, Lee SH, Oh DS, Kim YU. Melatonin inhibits neuronal dysfunction-associated with neuroinflammation by atopic psychological stress in NC/Nga atopic-like mouse models. J Pineal Res 2017; 63. [PMID: 28500766 DOI: 10.1111/jpi.12420] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Accepted: 05/05/2017] [Indexed: 01/03/2023]
Abstract
Atopic dermatitis (AD), also known as atopic eczema, is chronic pruritic skin disease. AD can increase psychological stress as well, increasing glucocorticoid release and exacerbating the associated symptoms. Chronic glucocorticoid elevation disturbs neuroendocrine signaling and can induce neuroinflammation, neurotoxicity, and cognitive impairment; however, it is unclear whether AD-related psychological stress elevates glucocorticoids enough to cause neuronal damage. Therefore, we assessed the effects of AD-induced stress in a mouse AD model. AD-related psychological stress increased astroglial and microglial activation, neuroinflammatory cytokine expression, and markers of neuronal loss. Notably, melatonin administration inhibited the development of skin lesions, scratching behavior, and serum IgE levels in the model mice, and additionally caused a significant reduction in corticotropin-releasing hormone responsiveness, and a significant reduction in neuronal damage. Finally, we produced similar results in a corticosterone-induced AD-like skin model. This is the first study to demonstrate that AD-related psychological stress increases neuroendocrine dysfunction, exacerbates neuroinflammation, and potentially accelerates other neurodegenerative disease states.
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Affiliation(s)
- Gunhyuk Park
- The K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon, Korea
| | - Seung Hoon Lee
- The K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon, Korea
| | - Dal-Seok Oh
- The K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon, Korea
| | - Yong-Ung Kim
- Department of Pharmaceutical Engineering, College of Biomedical Science, Daegu Haany University, Gyeongsan, Korea
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Ali SS, Abd El Wahab MG, Ayuob NN, Suliaman M. The antidepressant-like effect of Ocimum basilicum in an animal model of depression. Biotech Histochem 2017; 92:390-401. [DOI: 10.1080/10520295.2017.1323276] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Affiliation(s)
- SS Ali
- Anatomy Department, Faculty of Medicine, King Abdulaziz University
| | - MG Abd El Wahab
- Anatomy Department, Faculty of Medicine for Girls, Al Azhar University
- Faculty of Nurses, National Gard, King Saud University, Yousef Abdullatif Jameel Chair of Prophetic Medical Applications (YAJCPMA), Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - NN Ayuob
- Anatomy Department, Faculty of Medicine, King Abdulaziz University
- Histology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - M Suliaman
- Pharmacology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
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Dehydroepiandrosterone increases the number and dendrite maturation of doublecortin cells in the dentate gyrus of middle age male Wistar rats exposed to chronic mild stress. Behav Brain Res 2017; 321:137-147. [DOI: 10.1016/j.bbr.2017.01.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 12/30/2016] [Accepted: 01/02/2017] [Indexed: 01/11/2023]
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The effects of desipramine, fluoxetine, or tianeptine on changes in bulbar BDNF levels induced by chronic social instability stress and inflammation. Pharmacol Rep 2017; 69:520-525. [PMID: 31994095 DOI: 10.1016/j.pharep.2017.01.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Accepted: 01/09/2017] [Indexed: 01/05/2023]
Abstract
BACKGROUND Stress is a major predisposing factor in the development of psychiatric disorders and potential source of augmented inflammatory processes in the brain. Increasing body of evidence shows an important role of alterations in the olfactory bulbs (OBs) function in stress-related disorders. The aim of the present study was to investigate the impact of antidepressants on the alterations of brain-derived neurotrophic factor (BDNF) induced by lipopolysaccharide (LPS) in female rats subjected to chronic social instability stress (CSIS). METHODS 9 weeks old female rats were subjected to CSIS and injected ip once daily with desipramine (10 mg/kg), fluoxetine (5 mg/kg), or tianeptine (10 mg/kg) for 4 weeks. On the last day of the experiment, rats being at the estrus phase of cycle were injected ip with LPS (1 mg/kg) or saline. RESULTS The BDNF mRNA and protein levels were evaluated in the olfactory bulbs. and the BDNF protein levels were measured in plasma. A single LPS administration in the stressed rats resulted in significant decrease in the bulbar BDNF mRNA, but not in the protein level. Chronic administration of desipramine, fluoxetine, or tianeptine increased the BDNF mRNA expression and protein levels in the LPS-injected stressed rats. There was no effect of the studied antidepressants on the reduction of the plasma BDNF protein level induced by CSIS and LPS. CONCLUSIONS These results suggest that studied antidepressants were effective in inhibiting the impact of LPS on BDNF expression in the stressed rats what may be significant for beneficial action of this drugs.
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M30 Antagonizes Indoleamine 2,3-Dioxygenase Activation and Neurodegeneration Induced by Corticosterone in the Hippocampus. PLoS One 2016; 11:e0166966. [PMID: 27870896 PMCID: PMC5117770 DOI: 10.1371/journal.pone.0166966] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Accepted: 11/06/2016] [Indexed: 12/27/2022] Open
Abstract
Monoamine oxidases (MAO), downstream targets of glucocorticoid, maintain the turnover and homeostasis of monoamine neurotransmitters; yet, its pathophysiological role in monoamine deficiency, oxidative stress and neuroinflammation remains controversial. Protective effects of M30, a brain selective MAO inhibitor with iron-chelating antioxidant properties, have been shown in models of neurodegenerative diseases. This study aims to examine the neuroprotective mechanism of M30 against depressive-like behavior induced by corticosterone (CORT). Sprague-Dawley rats were given CORT subcutaneous injections with or without concomitant M30 administration for two weeks. CORT-treated rats exhibited depressive-like behavior with significant elevated levels of MAO activities, serotonin turnover, oxidative stress, neuroinflammation and apoptosis in the hippocampus with significant losses of synaptic proteins when compared to the control. The expression and activity of cytokine-responsive indoleamine 2,3-dioxygenase (IDO-1), a catabolic enzyme of serotonin and tryptophan, was significantly increased in the CORT-treated group with lowered levels of serotonin. Besides, CORT markedly reduced dendritic length and spine density. Remarkably, M30 administration neutralized the aberrant changes in the hippocampus and prevented the induction of depressive-like behavior induced by CORT. Our results suggest that M30 is neuroprotective against CORT-induced depression targeting elevated MAO activities that cause oxidative stress and neuroinflammation, resulting in IDO-1 activation, serotonin deficiency and neurodegeneration.
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Pollano A, Zalosnik MI, Durando PE, Suárez MM. Differential effects of tianeptine on the dorsal hippocampal volume of rats submitted to maternal separation followed by chronic unpredictable stress in adulthood. Stress 2016; 19:599-608. [PMID: 27604299 DOI: 10.1080/10253890.2016.1224842] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Early maternal separation (MS) may produce lasting effects in the dorsal hippocampus (DH) that can change its response to chronic stress in adulthood. Chronic stress affects DH morphology and function, but tianeptine (an anti-depressant) can reverse the stress-induced morphological impairments. Morphologic alterations of hippocampus can affect contextual memory. Therefore, we evaluated the effect of tianeptine in MS and chronically stressed rats on: 1) volume of the DH and its areas using stereology and 2) hippocampal-dependent memory using a fear conditioning test. Male Wistar rats were subjected to daily MS for 4.5 h between postnatal days (PND) 1-21, or to animal facility rearing (AFR). Between (PND) days 50 and 74, rats were exposed to chronic unpredictable stress and were treated daily with tianeptine (10 mg/kg) or vehicle, providing eight groups: AFR-unstressed/vehicle (n = 5 for stereology, n = 18 for fear conditioning test); AFR unstressed/tianeptine (n = 6 and n = 10); AFR-chronic stress/vehicle (n = 6 and n = 14); AFR-chronic stress/tianeptine (n = 6 and n = 10), MS-unstressed/vehicle (n = 5 and n = 19), MS-unstressed/tianeptine (n = 6 and n = 10), MS-chronic stress/vehicle (n = 6 and n = 18), and MS-chronic stress/tianeptine (n = 6 and n = 10). MS-chronic stress/tianeptine rats showed a diminished CA1 area than the corresponding MS-unstressed/tianeptine rats. The combination of stressors produced a freezing response similar to those of the control group during postconditioning. During retrieval, MS led to a diminished freezing response compared to the AFR-unstressed groups. Tianeptine had no effect on freezing behavior. Our results show that tianeptine can affect the CA1 area volume differently depending on the nature and quantity of stressors but cannot alter freezing to context.
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Affiliation(s)
- Antonella Pollano
- a Laboratorio de Fisiología Animal, Facultad de Ciencias Exactas, Físicas y Naturales , Universidad Nacional de Córdoba , Córdoba , Argentina
| | - María I Zalosnik
- a Laboratorio de Fisiología Animal, Facultad de Ciencias Exactas, Físicas y Naturales , Universidad Nacional de Córdoba , Córdoba , Argentina
| | - Patricia E Durando
- a Laboratorio de Fisiología Animal, Facultad de Ciencias Exactas, Físicas y Naturales , Universidad Nacional de Córdoba , Córdoba , Argentina
| | - Marta M Suárez
- a Laboratorio de Fisiología Animal, Facultad de Ciencias Exactas, Físicas y Naturales , Universidad Nacional de Córdoba , Córdoba , Argentina
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Kang E, Wen Z, Song H, Christian KM, Ming GL. Adult Neurogenesis and Psychiatric Disorders. Cold Spring Harb Perspect Biol 2016; 8:cshperspect.a019026. [PMID: 26801682 DOI: 10.1101/cshperspect.a019026] [Citation(s) in RCA: 138] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Psychiatric disorders continue to be among the most challenging disorders to diagnose and treat because there is no single genetic or anatomical locus that is causative for the disease. Current treatments are often blunt tools used to ameliorate the most severe symptoms, at the risk of disrupting functional neural systems. There is a critical need to develop new therapeutic strategies that can target circumscribed functional or anatomical domains of pathology. Adult hippocampal neurogenesis may be one such domain. Here, we review the evidence suggesting that adult hippocampal neurogenesis plays a role in emotional regulation and forms of learning and memory that include temporal and spatial memory encoding and context discrimination, and that its dysregulation is associated with psychiatric disorders, such as affective disorders, schizophrenia, and drug addiction. Further, adult neurogenesis has proven to be an effective model to investigate basic processes of neuronal development and converging evidence suggests that aberrant neural development may be an etiological factor, even in late-onset diseases. Constitutive neurogenesis in the hippocampus of the mature brain reflects large-scale plasticity unique to this region and could be a potential hub for modulation of a subset of cognitive and affective behaviors that are affected by multiple psychiatric disorders.
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Affiliation(s)
- Eunchai Kang
- Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
| | - Zhexing Wen
- Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
| | - Hongjun Song
- Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
| | - Kimberly M Christian
- Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
| | - Guo-Li Ming
- Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
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García-Fuster MJ, García-Sevilla JA. Effects of anti-depressant treatments on FADD and p-FADD protein in rat brain cortex: enhanced anti-apoptotic p-FADD/FADD ratio after chronic desipramine and fluoxetine administration. Psychopharmacology (Berl) 2016; 233:2955-71. [PMID: 27259485 DOI: 10.1007/s00213-016-4342-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2016] [Accepted: 05/20/2016] [Indexed: 12/27/2022]
Abstract
RATIONALE Fas-associated death domain (FADD) is an adaptor of death receptors that can also induce anti-apoptotic actions through its phosphorylated form (p-FADD). Activation of monoamine receptors, indirect targets of classic anti-depressant drugs (ADs), reduced FADD and increased p-FADD and p-FADD/FADD ratio in brain. OBJECTIVES To ascertain whether ADs, which indirectly regulate monoamine receptors, modulate FADD protein forms to promote anti-apoptotic actions. METHODS The effects of selected norepinephrine transporter (NET), serotonin transporter (SERT), monoamine oxidase (MAO) inhibitors, atypical ADs, and electroconvulsive shock (ECS) or behavioral procedures (forced swim test, FST) on FADD forms and pro-survival FADD-like interleukin-1β-converting enzyme-inhibitory protein (FLIP-L) and phosphoprotein enriched in astrocytes of 15 kDa (p-PEA-15) contents were assessed in rat brain cortex by western blot analysis. RESULTS Acute NET (e.g., nisoxetine) but not SERT (e.g., fluoxetine) inhibitors decreased cortical FADD (up to 37 %) and increased p-FADD/FADD ratio (up to 1.9-fold). Nisoxetine effects were prevented by α2-antagonist RX-821002, suggesting the involvement of presynaptic α2-autoreceptors. Immobility time in the FST correlated with increases of pro-apoptotic FADD and decreases of anti-apoptotic p-FADD. The MAO-A/B inhibitor phenelzine decreased FADD (up to 33 %) and increased p-FADD (up to 65 %) and p-FADD/FADD (up to 2.4-fold). Other MAO inhibitors (clorgyline, Ro 41-1049, rasagiline), atypical ADs (ketamine and mirtazapine), or ECS did not modulate cortical FADD. Chronic (14 days) desipramine and fluoxetine, but not phenelzine, increased p-FADD (up to 59 %), p-FADD/FADD ratio (up to 1.8-fold), and pro-survival p-PEA-15 (up to 46 %) in rat brain cortex. CONCLUSIONS Multifunctional FADD protein, through an increased p-FADD/FADD ratio, could participate in the mechanisms of anti-apoptotic actions induced by ADs.
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Affiliation(s)
- M Julia García-Fuster
- Neurobiology of Drug Abuse Group, IUNICS/IdISPa, University of the Balearic Islands, Cra. Valldemossa km 7.5, E-07122, Palma de Mallorca, Spain. .,Redes Temáticas de Investigación Cooperativa en Salud-Red de Trastornos Adictivos (RETICS-RTA), ISCIII, Madrid, Spain.
| | - Jesús A García-Sevilla
- Laboratory of Neuropharmacology, IUNICS/IdISPa, University of the Balearic Islands, Palma de Mallorca, Spain.,Redes Temáticas de Investigación Cooperativa en Salud-Red de Trastornos Adictivos (RETICS-RTA), ISCIII, Madrid, Spain
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The antidepressant effect of musk in an animal model of depression: a histopathological study. Cell Tissue Res 2016; 366:271-284. [DOI: 10.1007/s00441-016-2468-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Accepted: 07/04/2016] [Indexed: 11/25/2022]
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Evaluation of the antidepressant-like effect of musk in an animal model of depression: how it works. Anat Sci Int 2016; 92:539-553. [PMID: 27444866 DOI: 10.1007/s12565-016-0357-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Accepted: 07/08/2016] [Indexed: 12/13/2022]
Abstract
Depression has become a common public health problem that is showing increasing prevalence. Slow onset of action, low response rates and drug resistance are potential limitations of the current antidepressant drugs. Alternative therapy using natural substances, specifically aromatherapy, is currently tried to treat depression. This work aimed to assess the efficacy of musk in relieving the behavioral, biochemical and hippocampal histopathological changes induced by exposure to chronic mild stress in mice and explore the possible mechanism behind this antidepressant-like effect. Forty male albino mice were divided into four groups (n = 10): control, a group exposed to chronic unpredictable mild stress (CUMS) and two groups exposed to CUMS and then treated with fluoxetine or musk. Behavioral changes and serum corticosterone levels were assessed at the end of the experiment. Protein and gene expressions of brain-derived neurotropic factor (BDNF) and glucocorticoid receptors (GRs) in the hippocampus were assessed using ELISA and real-time RT-PCR, respectively. Histopathological examination of the hippocampus and immunohistochemical techniques using glial fibrillary acidic protein (GFAP), Ki67, caspase-3, BDNF and GR were performed. Inhalation of musk had an antidepressant-like effect in an animal model of depression. Musk alleviated the behavioral changes and elevated serum corticosterone levels induced by exposure to chronic stress. It reduced the hippocampal neuronal apoptosis and stimulated neurogenesis in the dentate gyrus. Musk's action may be related to the upregulation of hippocampal GR and BDNF expressions. Musk is considered a potential antidepressant so it is advisable to assess its efficacy in treating depressed patient.
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Seo MK, McIntyre RS, Cho HY, Lee CH, Park SW, Mansur RB, Kim GM, Baek JH, Woo YS, Lee JG, Kim YH. Tianeptine induces mTORC1 activation in rat hippocampal neurons under toxic conditions. Psychopharmacology (Berl) 2016; 233:2617-27. [PMID: 27129862 DOI: 10.1007/s00213-016-4309-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Accepted: 04/22/2016] [Indexed: 12/23/2022]
Abstract
RATIONALE Recent studies have demonstrated that mTORC1 activation may be related to antidepressant action. However, the relationship between mTORC1 signaling activation and currently prescribed antidepressants remains unclear. OBJECTIVE The aim of the present study was to determine whether alterations in mTORC1 signaling are observable following treatment with tianeptine under toxic conditions induced by B27 deprivation. Additionally, we investigated whether this drug affects synaptic proteins, neurite outgrowth, and spine density via mTORC1 signaling. METHODS Using Western blotting, we measured the phosphorylation levels of mTORC1, 4E-BP-1, p70S6K, Akt, and ERK in rat primary hippocampal neurons. Changes in BDNF, dendritic outgrowth, spine density, and synaptic proteins (PSD-95, synaptophysin, and GluR1) were measured. RESULTS Tianeptine significantly increased the phosphorylation of mTORC1, 4E-BP-1, p70S6K, Akt, and ERK. The increase in mTOR phosphorylation was blocked by the PI3K, MEK, and mTORC1 inhibitors. Tianeptine increased BDNF, dendritic outgrowth, spine density, and synaptic proteins; all of these effects were blocked by the mTORC1 inhibitor. CONCLUSIONS In this study, we demonstrated that tianeptine activates the mTORC1 signaling pathway and increases dendritic outgrowth, spine density, and synaptic proteins through mTORC1 signaling under toxic conditions in rat primary hippocampal neurons.
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Affiliation(s)
- Mi Kyoung Seo
- Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea
| | - Roger S McIntyre
- Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Hye Yeon Cho
- Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea
| | - Chan Hong Lee
- Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea
| | - Sung Woo Park
- Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea
- Department of Health Science and Technology, Graduate School, Inje University, Busan, Republic of Korea
| | - Rodrigo B Mansur
- Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Gyung-Mee Kim
- Department of Psychiatry, School of Medicine, Haeundae Paik Hospital, Inje University, Busan, Republic of Korea
| | - Jun Hyung Baek
- Department of Psychiatry, School of Medicine, Haeundae Paik Hospital, Inje University, Busan, Republic of Korea
| | - Young Sup Woo
- Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jung Goo Lee
- Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea.
- Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada.
- Department of Health Science and Technology, Graduate School, Inje University, Busan, Republic of Korea.
- Department of Psychiatry, School of Medicine, Haeundae Paik Hospital, Inje University, Busan, Republic of Korea.
- Department of Psychiatry, Inje University Haeundae Paik Hospital, 1435, Jwa-dong, Haeundae-gu, Busan, 612-030, Republic of Korea.
| | - Young Hoon Kim
- Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea.
- Department of Health Science and Technology, Graduate School, Inje University, Busan, Republic of Korea.
- Department of Psychiatry, School of Medicine, Haeundae Paik Hospital, Inje University, Busan, Republic of Korea.
- Department of Psychiatry, Inje University Haeundae Paik Hospital, 1435, Jwa-dong, Haeundae-gu, Busan, 612-030, Republic of Korea.
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Different effects of prenatal stress on ERK2/CREB/Bcl-2 expression in the hippocampus and the prefrontal cortex of adult offspring rats. Neuroreport 2016; 27:600-4. [DOI: 10.1097/wnr.0000000000000581] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
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High activity of the stress promoter contributes to susceptibility to stress in the tree shrew. Sci Rep 2016; 6:24905. [PMID: 27125313 PMCID: PMC4850381 DOI: 10.1038/srep24905] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Accepted: 04/06/2016] [Indexed: 12/28/2022] Open
Abstract
Stress is increasingly present in everyday life in our fast-paced society and involved in the pathogenesis of many psychiatric diseases. Corticotrophin-releasing-hormone (CRH) plays a pivotal role in regulating the stress responses. The tree shrews are highly vulnerable to stress which makes them the promising animal models for studying stress responses. However, the mechanisms underlying their high stress-susceptibility remained unknown. Here we confirmed that cortisol was the dominate corticosteroid in tree shrew and was significantly increased after acute stress. Our study showed that the function of tree shrew CRH - hypothalamic-pituitary-adrenal (HPA) axis was nearly identical to human that contributed little to their hyper-responsiveness to stress. Using CRH transcriptional regulation analysis we discovered a peculiar active glucocorticoid receptor response element (aGRE) site within the tree shrew CRH promoter, which continued to recruit co-activators including SRC-1 (steroid receptor co-activator-1) to promote CRH transcription under basal or forskolin/dexamethasone treatment conditions. Basal CRH mRNA increased when the aGRE was knocked into the CRH promoter in human HeLa cells using CAS9/CRISPR. The aGRE functioned critically to form the "Stress promoter" that contributed to the higher CRH expression and susceptibility to stress. These findings implicated novel molecular bases of the stress-related diseases in specific populations.
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Animal models of major depression and their clinical implications. Prog Neuropsychopharmacol Biol Psychiatry 2016; 64:293-310. [PMID: 25891248 DOI: 10.1016/j.pnpbp.2015.04.004] [Citation(s) in RCA: 264] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Revised: 03/09/2015] [Accepted: 04/12/2015] [Indexed: 12/12/2022]
Abstract
Major depressive disorder is a common, complex, and potentially life-threatening mental disorder that imposes a severe social and economic burden worldwide. Over the years, numerous animal models have been established to elucidate pathophysiology that underlies depression and to test novel antidepressant treatment strategies. Despite these substantial efforts, the animal models available currently are of limited utility for these purposes, probably because none of the models mimics this complex disorder fully. It is presumable that psychiatric illnesses, such as affective disorders, are related to the complexity of the human brain. Here, we summarize the animal models that are used most commonly for depression, and discuss their advantages and limitations. We discuss genetic models, including the recently developed optogenetic tools and the stress models, such as the social stress, chronic mild stress, learned helplessness, and early-life stress paradigms. Moreover, we summarize briefly the olfactory bulbectomy model, as well as models that are based on pharmacological manipulations and disruption of the circadian rhythm. Finally, we highlight common misinterpretations and often-neglected important issues in this field.
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Parésys L, Hoffmann K, Froger N, Bianchi M, Villey I, Baulieu EE, Fuchs E. Effects of the Synthetic Neurosteroid: 3β-Methoxypregnenolone (MAP4343) on Behavioral and Physiological Alterations Provoked by Chronic Psychosocial Stress in Tree Shrews. Int J Neuropsychopharmacol 2015; 19:pyv119. [PMID: 26476437 PMCID: PMC4851265 DOI: 10.1093/ijnp/pyv119] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Accepted: 10/14/2015] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Most currently available active antidepressant drugs are selective serotonin/noradrenaline reuptake inhibitors. However, as their clinical efficacy is not immediate, long-term administration is often accompanied by substantial side effects, and numerous patients remain non- or partial responders. We have recently found that the synthetic neurosteroid derivative 3β-methoxypregnenolone, which binds to the microtubule-associated protein-2, can provide a novel therapeutic approach in experimental model of depressive disorders in rats. To further validate the antidepressant-like efficacy of 3β-methoxypregnenolone, we investigated effects of a longer treatment (4-week oral administration; 50mg/kg/d) in a nonrodent species, the tree shrew, exposed to psychosocial stress that elicits close-to-human alterations observed in patients with depressive disorders. METHODS During the experimental period, physiological parameters were registered, including core body temperature and electroencephalogram, while animals were videotaped to analyze their avoidance behavior. Morning urine samples were collected for measurements of cortisol and noradrenaline levels. RESULTS We found that treatment with 3β-methoxypregnenolone abolished stress-triggered avoidance behavior and prevented hormone hypersecretion, hypothermia, and sleep disturbances, further suggesting its antidepressant-like efficacy. Comparative treatment with fluoxetine also prevented some of the physiological alterations, while the hypersecretion of cortisol and sleep disturbances were not or partially restored by fluoxetine, suggesting a better efficacy of 3β-methoxypregnenolone. Alpha-tubulin isoforms were measured in hippocampi: we found that 3β-methoxypregnenolone reversed the specific decrease in acetylation of α-tubulin induced by psychosocial stress, while it did not modify the psychosocial stress-elicited reduction of tyrosinated α-tubulin. CONCLUSIONS Taken together, these data strongly suggest a potent antidepressant-like effect of 3β-methoxypregnenolone on translational parameters.
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Affiliation(s)
| | | | - Nicolas Froger
- MAPREG SAS, Le Kremlin-Bicêtre, France (Drs Parésys, Froger, Bianchi, Villey, and Baulieu); German Primate Center, Göttingen, Germany (Drs Hoffmann and Fuchs).
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Effects of long-term agomelatine treatment on the cognitive performance and hippocampal plasticity of adult rats. Behav Pharmacol 2015; 26:469-80. [DOI: 10.1097/fbp.0000000000000153] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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Halaris A. Neurological disorders, depression and inflammation: is there a common link? FUTURE NEUROLOGY 2015. [DOI: 10.2217/fnl.15.18] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
To understand the origin of co-morbidity between neurological disorders and depressive illness, a multifactorial model is in order. Diverse approaches have been undertaken to elucidate the co-morbidity. Of these, the concept that inflammatory processes contribute to brain-related pathologies has been gaining traction. Inflammatory processes have been identified in most, if not all, neurological conditions. Similarly, major depressive disorder has been associated with a chronic proinflammatory status. Activation of the immune response can alter neurotransmission leading, among others, to serotonin deficiency, and increased production of neurotoxic substances contributing to primary disease progression. Therefore, inflammatory factors might serve as biomarkers to predict and ultimately prevent the development and progression of neuropsychiatric disorders as well as to identify the most efficacious treatments.
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Affiliation(s)
- Angelos Halaris
- Professor of Psychiatry, Department of Psychiatry & Behavioral Sciences, Loyola University Chicago Stritch School of Medicine, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA
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Chronic corticosterone exposure reduces hippocampal astrocyte structural plasticity and induces hippocampal atrophy in mice. Neurosci Lett 2015; 592:76-81. [DOI: 10.1016/j.neulet.2015.03.006] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Revised: 02/25/2015] [Accepted: 03/02/2015] [Indexed: 12/15/2022]
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Nowacka MM, Paul-Samojedny M, Bielecka AM, Obuchowicz E. Chronic social instability stress enhances vulnerability of BDNF response to LPS in the limbic structures of female rats: A protective role of antidepressants. Neurosci Res 2014; 88:74-83. [DOI: 10.1016/j.neures.2014.08.008] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2014] [Revised: 07/31/2014] [Accepted: 08/21/2014] [Indexed: 01/06/2023]
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Czéh B, Varga ZKK, Henningsen K, Kovács GL, Miseta A, Wiborg O. Chronic stress reduces the number of GABAergic interneurons in the adult rat hippocampus, dorsal-ventral and region-specific differences. Hippocampus 2014; 25:393-405. [PMID: 25331166 DOI: 10.1002/hipo.22382] [Citation(s) in RCA: 109] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/09/2014] [Indexed: 11/05/2022]
Abstract
Major depressive disorder is a common and complex mental disorder with unknown etiology. GABAergic dysfunction is likely to contribute to the pathophysiology since disrupted GABAergic systems are well documented in depressed patients. Here we studied structural changes in the hippocampal GABAergic network using the chronic mild stress (CMS) model, as one of the best validated animal models for depression. Rats were subjected to 9 weeks of daily stress and behaviorally characterized using the sucrose consumption test into anhedonic and resilient animals based on their response to stress. Different subtypes of GABAergic interneurons were visualized by immunohistochemistry using antibodies for parvalbumin (PV), calretinin (CR), calbindin (CB), cholecystokinin (CCK), somatostatin (SOM), and neuropeptide Y (NPY). We used an unbiased quantification method to systematically count labeled cells in different subareas of the dorsal and ventral hippocampus. Chronic stress reduced the number of specific interneurons in distinct hippocampal subregions significantly. PV+ and CR+ neurons were reduced in all dorsal subareas, whereas in the ventral part only the CA1 was affected. Stress had the most pronounced effect on the NPY+ and SOM+ cells and reduced their number in almost all dorsal and ventral subareas. Stress had no effect on the CCK+ and CB+ interneurons. In most cases the effect of stress was irrespective to the behavioral phenotype. However, in a few specific areas the number of SOM+, NPY+, and CR+ neurons were significantly reduced in anhedonic animals compared to the resilient group. Overall, these data clearly demonstrate that chronic stress affects the structural integrity of specific GABAergic neuronal subpopulations and this should also affect the functioning of these hippocampal GABAergic networks.
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Affiliation(s)
- Boldizsár Czéh
- Institute of Laboratory Medicine, Faculty of Medicine, University of Pécs, 7624, Pécs, Hungary; Structural Neurobiology Research Group, Szentágothai János Research Center, University of Pécs, 7624, Pécs, Hungary; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, 8240, Risskov, Denmark
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45
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Li YH, Zhang CH, Qiu J, Wang SE, Hu SY, Huang X, Xie Y, Wang Y, Cheng TL. Antidepressant-like effects of Chaihu-Shugan-San via SAPK/JNK signal transduction in rat models of depression. Pharmacogn Mag 2014; 10:271-7. [PMID: 25210314 PMCID: PMC4159920 DOI: 10.4103/0973-1296.137367] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2013] [Revised: 08/17/2013] [Accepted: 07/24/2014] [Indexed: 12/20/2022] Open
Abstract
Background: Chaihu-Shugan-San (CHSGS), a traditional Chinese medicinal herbal formula, registered in Jingyue Quanshu, has been indicated that oral administration of the extract from it can remit depressive disorder. C-Jun amino-terminal kinase (JNK/SAPK) signal transduction plays a key role in the apoptosis of nerve cells, be reported closely correlated with depression. This study was designed to investigate CHSGS antidepressant-like effects in rat models of depression and probe its possible mechanism. Materials and Methods: The classical experimental depression model chronic mild unpredictable stress (CMUS) was used to evaluate the antidepressant-like effects of CHSGS. The extracts were administered orally for 14 days, while the parallel positive control was given at the same time using fluoxetine hydrochloride. The expressions of JNK in the hippocampus were detected by real-time fluorescent quantitation PCR and Western blot assay. Results: Intragastric administration of CHSGS for 14 days caused a significant improvement of weight and locomotor activity in the open-field test. In addition, CHSGS treatment inhibited the expressions of JNK in the hippocampus tissue in CMUS rats. Conclusion: CHSGS could obviously improve the depressive state of the model rats and its mechanism may be correlated with regulating the expressions of JNK in the hippocampus.
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Affiliation(s)
- Yun-Hui Li
- Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Traditional Chinese Medicine Gan Organ of SATCM, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, PR China
| | - Chun-Hu Zhang
- Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Traditional Chinese Medicine Gan Organ of SATCM, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, PR China
| | - Juan Qiu
- Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Traditional Chinese Medicine Gan Organ of SATCM, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, PR China
| | - Su-E Wang
- Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Traditional Chinese Medicine Gan Organ of SATCM, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, PR China
| | - Sui-Yu Hu
- Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Traditional Chinese Medicine Gan Organ of SATCM, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, PR China
| | - Xi Huang
- Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Traditional Chinese Medicine Gan Organ of SATCM, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, PR China
| | - Ying Xie
- Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Traditional Chinese Medicine Gan Organ of SATCM, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, PR China
| | - Yang Wang
- Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Traditional Chinese Medicine Gan Organ of SATCM, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, PR China
| | - Tian-Li Cheng
- Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Traditional Chinese Medicine Gan Organ of SATCM, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, PR China
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46
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Baicalin reverse AMPA receptor expression and neuron apoptosis in chronic unpredictable mild stress rats. Biochem Biophys Res Commun 2014; 451:467-72. [DOI: 10.1016/j.bbrc.2014.07.041] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2014] [Accepted: 07/07/2014] [Indexed: 11/18/2022]
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47
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Kolla BP, Mansukhani MP. Antidepressants trigger an early clinical presentation of REM sleep behavior disorder: the jury is still out. Sleep 2014; 37:1393. [PMID: 25083020 DOI: 10.5665/sleep.3938] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
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48
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FADD adaptor and PEA-15/ERK1/2 partners in major depression and schizophrenia postmortem brains: basal contents and effects of psychotropic treatments. Neuroscience 2014; 277:541-51. [PMID: 25075716 DOI: 10.1016/j.neuroscience.2014.07.027] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Revised: 06/26/2014] [Accepted: 07/18/2014] [Indexed: 01/05/2023]
Abstract
Enhanced brain apoptosis (neurons and glia) may be involved in major depression (MD) and schizophrenia (SZ), mainly through the activation of the intrinsic (mitochondrial) apoptotic pathway. In the extrinsic death pathway, pro-apoptotic Fas-associated death domain (FADD) adaptor and its non-apoptotic p-Ser194 FADD form have critical roles interacting with other death regulators such as phosphoprotein enriched in astrocytes of 15 kDa (PEA-15) and extracellular signal-regulated kinase (ERK). The basal status of FADD (protein and messenger RNA (mRNA)) and the effects of psychotropic drugs (detected in blood/urine samples) were first assessed in postmortem prefrontal cortex of MD and SZ subjects (including a non-MD/SZ suicide group). In MD, p-FADD, but not total FADD (and mRNA), was increased (26%, n=24; all MD subjects) as well as p-FADD/FADD ratio (a pro-survival marker) in antidepressant-free MD subjects (50%, n=10). In contrast, cortical FADD (and mRNA), p-FADD, and p-FADD/FADD were not altered in SZ brains (n=21) regardless of antipsychotic medications (except enhanced mRNA in treated subjects). Similar negative results were quantified in the non-MD/SZ suicide group. In MD, the regulation of multifunctional PEA-15 (i.e., p-Ser116 PEA-15 blocks pro-apoptotic FADD and PEA-15 prevents pro-survival ERK action) and the modulation of p-ERK1/2 were also investigated. Cortical p-PEA-15 was not changed whereas PEA-15 was increased mainly in antidepressant-treated subjects (16-20%). Interestingly, cortical p-ERK1/2/ERK1/2 ratio was reduced (33%) in antidepressant-free when compared to antidepressant-treated MD subjects. The neurochemical adaptations of brain FADD (increased p-FADD and pro-survival p-FADD/FADD ratio), as well as its interaction with PEA-15, could play a major role to counteract the known activation of the mitochondrial apoptotic pathway in MD.
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49
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Zhang Y, Liu W, Zhou Y, Ma C, Li S, Cong B. Endoplasmic reticulum stress is involved in restraint stress-induced hippocampal apoptosis and cognitive impairments in rats. Physiol Behav 2014; 131:41-8. [DOI: 10.1016/j.physbeh.2014.04.014] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2013] [Revised: 02/25/2014] [Accepted: 04/04/2014] [Indexed: 01/05/2023]
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50
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Improvement in subjective and objective neurocognitive functions in patients with major depressive disorder: a 12-week, multicenter, randomized trial of tianeptine versus escitalopram, the CAMPION study. J Clin Psychopharmacol 2014; 34:218-25. [PMID: 24525660 DOI: 10.1097/jcp.0000000000000072] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Although many patients with major depressive disorder (MDD) complain of neurocognitive impairment, the effects of antidepressant medications on neurocognitive functions remain unclear. This study compares neurocognitive effects of tianeptine and escitalopram in MDD. Patients with MDD (N = 164) were randomly assigned in a 1:1 ratio to either tianeptine (37.5 mg/d) or escitalopram (10 mg/d) for 12 weeks. Outcome measures included clinical improvement, subjective cognitive impairment on memory and concentration, the Mini-Mental State Examination, the Continuous Performance Test, the Verbal Learning Test, and the Raven Progressive Matrices, assessed every 4 weeks. After 12 weeks, the tianeptine group showed significant improvement in commission errors (P = 0.002), verbal immediate memory (P < 0.0001), Mini-Mental State Examination (P < 0.0001), delayed memory (P < 0.0001), and reasoning ability (P = 0.0010), whereas the escitalopram group improved in delayed memory and reasoning ability but not in the other measures. Both groups significantly improved in subjective cognitive impairment in memory (P < 0.0001) and concentration (P < 0.0001). Mixed effects model repeated measures analyses revealed that the tianeptine group had a significant improvement in scores of commission errors (F = 6.64, P = 0.011) and verbal immediate memory (F = 4.39, P = 0.038) from baseline to 12 weeks, compared with the escitalopram group, after controlling for age, sex, education years, baseline scores, and changes of depression severity. The treatment of MDD with tianeptine led to more improvements in neurocognitive functions, especially in commission errors and verbal immediate memory, compared with escitalopram, after controlling for changes in depression severity. Both drugs improved subjective cognitive impairment of memory and concentration.
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