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Li G, Huang L, Gu D, Wang P, Yi L, Kuang W, Zhang Y, Zhang J, Liu D, Shi Q, Tang H, Sun J, Zeng G, Peng X, Wang J. Activity-based chemical proteomics reveals caffeic acid ameliorates pentylenetetrazol-induced seizures by covalently targeting aconitate decarboxylase 1. Cell Commun Signal 2025; 23:62. [PMID: 39901156 PMCID: PMC11792687 DOI: 10.1186/s12964-024-01739-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 07/04/2024] [Indexed: 02/05/2025] Open
Abstract
BACKGROUND Epilepsy is a neurological disorder characterized by recurrent seizures, tightly associated with neuroinflammation. Activation of inflammatory cells and molecules in damaged nervous tissues plays a pivotal role in epilepsy. Caffeic acid, one of the most abundant polyphenols in coffee, has shown potent protective effects as a phytomedicine in various neurological disorders. However, the direct protein targets and exact molecular mechanisms of caffeic acid in epilepsy, remain largely elusive. PURPOSE This study aimed to explore the protective effects of caffeic acid in epilepsy and elucidate its underlying mechanism. METHODS In this study, we established pentylenetetrazol-induced acute and kindling models of seizures. Additionally, a BV2 microglial cellular inflammation model was established by lipopolysaccharide stimulation. The potential direct protein targets of caffeic acid in BV2 cells were analyzed using an activity-based protein profiling (ABPP) with a caffeic acid probe. Various methods such as pull-down assay, immunofluorescence and cellular heat transfer assays were used for experimental validation. The anti-inflammatory effects of caffeic acid in LPS-activated BV2 cells was proved by knocking down the target protein. RESULTS Here, we found that caffeic acid exhibits antiepileptic effects in pentylenetetrazol-induced epilepsy mice and exerts anti-neuroinflammation effect in vivo and in vitro. Besides, we discovered that caffeic acid directly binds to aconitate decarboxylase 1 and influenced its enzymatic activity. Moreover, we indicated that caffeic acid exhibits anti-neuroinflammation effect through aconitate decarboxylase 1 mediated PERK-NF-κB pathway in vitro. CONCLUSION In summary, this study elucidates, for the first time, the potential antiepileptic targets and mechanism of action of caffeic acid using the ABPP strategy. Our study provides evidence supporting the utilization of caffeic acid as a promising therapeutic agent for treating epilepsy and neuroinflammation-related disorders.
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Affiliation(s)
- Guanjun Li
- Department of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, China
| | - Ling Huang
- Department of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, China
| | - Di Gu
- Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, Guangdong, China
| | - Peili Wang
- Xiyuan Hospital, National Clinical Research Center for Chinese Medicine Cardiology, Academy of Chinese Medical Sciences, Beijing, China
| | - Letai Yi
- Inner Mongolia Medical University, 010000, Hohhot, Inner Mongolia, China
| | - Wenhua Kuang
- Department of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, China
| | - Ying Zhang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700, Beijing, China
| | - Junzhe Zhang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700, Beijing, China
| | - Dandan Liu
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700, Beijing, China
| | - Qiaoli Shi
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700, Beijing, China
| | - Huan Tang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700, Beijing, China
| | - Jichao Sun
- Department of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, China.
| | - Guohua Zeng
- Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, Guangdong, China.
| | - Xin Peng
- Ningbo Municipal Hospital of TCM, Affiliated Hospital of Zhejiang Chinese Medical University, 315000, Ningbo, Zhejiang, China.
| | - Jigang Wang
- Department of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, China.
- Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, Guangdong, China.
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700, Beijing, China.
- State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, 475004, Kaifeng, China.
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Wang HT, Lu ST, Xia ZH, Xu T, Zou WY, Sun MQ. Ciliary neurotrophic factor activation of astrocytes mediates neuronal damage via the IL‑6/IL‑6R pathway. Mol Med Rep 2025; 31:32. [PMID: 39575470 PMCID: PMC11600100 DOI: 10.3892/mmr.2024.13396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 09/24/2024] [Indexed: 11/29/2024] Open
Abstract
The occurrence of epilepsy is a spontaneous and recurring process due to abnormal neuronal firing in the brain. Epilepsy is understood to be caused by an imbalance between excitatory and inhibitory neurotransmitters in the neural network. The close association between astrocytes and synapses can regulate the excitability of neurons through the clearance of neurotransmitters. Therefore, the abnormal function of astrocytes can lead to the onset and development of epilepsy. The onset of epilepsy can produce a large number of inflammatory mediators, which can aggravate epileptic seizures, leading to a vicious cycle. Neurons and glial cells interact to promote the onset and maintenance of epilepsy, but the specific underlying molecular mechanisms need to be further studied. Ciliary neurotrophic factor (CNTF) belongs to the IL‑6 cytokine family and is mainly secreted by astrocytes and Schwann cells. In the normal physiological state, CNTF levels are low, but in an epileptic state, CNTF levels in the serum and tears of patients are elevated. Astrocyte activation plays an important role in epileptic seizures. CNTF activates astrocytes to produce a variety of secreted proteins, which are secreted into the astrocyte culture medium (ACM), thus forming a distinct culture medium (CNTF‑ACM) that can be used to study the effect of astrocytes on neurons in vitro. CNTF‑activated astrocytes increase the secretion of the pro‑inflammatory factor IL‑6. In the present study, CNTF‑ACM was applied to primary cerebral cortical neurons to observe the specific effects of IL‑6 in CNTF‑ACM on neuronal activity and excitability. The results suggested that CNTF‑ACM can reduce neuronal activity via the IL‑6/IL‑6R pathway, promote neuronal apoptosis, increase Ca2+ inflow, activate the large conductance calcium‑activated potassium channel and enhance neuronal excitability. The results of the present study further revealed the functional changes of astrocytes after CNTF activated astrocytes and the effects on neuronal activity and excitability, thereby providing new experimental evidence for the role of communication between astrocytes and neurons in the mechanism of epileptic seizures.
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Affiliation(s)
- Hong-Tao Wang
- Anhui Province Key Laboratory of Immunology in Chronic Diseases, Bengbu Medical University, Bengbu, Anhui 233030, P.R. China
| | - Si-Tong Lu
- Anhui Province Key Laboratory of Immunology in Chronic Diseases, Bengbu Medical University, Bengbu, Anhui 233030, P.R. China
- Department of Histology and Embryology, Bengbu Medical University, Bengbu, Anhui 233030, P.R. China
- Department of Stomatology, Wuhan College of Arts and Science, Wuhan, Hubei 430101, P.R. China
| | - Zhi-Hui Xia
- Anhui Province Key Laboratory of Immunology in Chronic Diseases, Bengbu Medical University, Bengbu, Anhui 233030, P.R. China
- Department of Histology and Embryology, Bengbu Medical University, Bengbu, Anhui 233030, P.R. China
| | - Tao Xu
- Anhui Province Key Laboratory of Immunology in Chronic Diseases, Bengbu Medical University, Bengbu, Anhui 233030, P.R. China
- Department of Clinical Laboratory and Diagnostics, Laboratory Medicine College, Bengbu Medical University, Bengbu, Anhui, 233030, P.R. China
| | - Wei-Yan Zou
- Anhui Province Key Laboratory of Immunology in Chronic Diseases, Bengbu Medical University, Bengbu, Anhui 233030, P.R. China
- Department of Histology and Embryology, Bengbu Medical University, Bengbu, Anhui 233030, P.R. China
| | - Mei-Qun Sun
- Anhui Province Key Laboratory of Immunology in Chronic Diseases, Bengbu Medical University, Bengbu, Anhui 233030, P.R. China
- Department of Histology and Embryology, Bengbu Medical University, Bengbu, Anhui 233030, P.R. China
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Chen XM, Zhang S, Gao SQ, Xu M. Interleukin-6 in epilepsy and its neuropsychiatric comorbidities: How to bridge the gap. World J Psychiatry 2025; 15:100297. [PMID: 39831011 PMCID: PMC11684222 DOI: 10.5498/wjp.v15.i1.100297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 10/31/2024] [Accepted: 11/21/2024] [Indexed: 12/18/2024] Open
Abstract
There is growing evidence that interleukin (IL)-6 plays an important role in neurological and psychiatric disorders. This editorial comments on the study published in the recent issue of the World Journal of Psychiatry, which employed Mendelian randomization to identify a causal relationship between IL-6 receptor blockade and decreased epilepsy incidence. The purpose of this editorial is to highlight the dual effects of IL-6 in epilepsy and its related neuropsychiatric comorbidities. IL-6 plays a critical role in the facilitation of epileptogenesis and maintenance of epileptic seizures and is implicated in neuroinflammatory processes associated with epilepsy. Furthermore, IL-6 significantly influences mood regulation and cognitive dysfunction in patients with epilepsy, highlighting its involvement in neuropsychiatric comorbidities. In summary, IL-6 is not only a pivotal factor in the pathogenesis of epilepsy but also significantly contributes to the emergence of epilepsy-related neuropsychiatric complications. Future research should prioritize elucidating the specific mechanisms by which IL-6 operates across different subtypes, stages and neuropsychiatric comorbidities of epilepsy, with the aim of developing more precise and effective interventions. Furthermore, the potential of IL-6 as a biomarker for the early diagnosis and prognosis of epilepsy warrants further investigation.
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Affiliation(s)
- Xiao-Man Chen
- Department of Neurology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Shuo Zhang
- Department of Neurology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Shi-Qi Gao
- Department of Rehabilitation, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110004, Liaoning Province, China
| | - Michael Xu
- International Education School, China Medical University, Shenyang 110004, Liaoning Province, China
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Li X, Guo S, Sun Y, Ding J, Chen C, Wu Y, Li P, Sun T, Wang X. GABRG2 mutations in genetic epilepsy with febrile seizures plus: structure, roles, and molecular genetics. J Transl Med 2024; 22:767. [PMID: 39143639 PMCID: PMC11323400 DOI: 10.1186/s12967-024-05387-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 06/10/2024] [Indexed: 08/16/2024] Open
Abstract
Genetic epilepsy with febrile seizures plus (GEFS+) is a genetic epilepsy syndrome characterized by a marked hereditary tendency inherited as an autosomal dominant trait. Patients with GEFS+ may develop typical febrile seizures (FS), while generalized tonic-clonic seizures (GTCSs) with fever commonly occur between 3 months and 6 years of age, which is generally followed by febrile seizure plus (FS+), with or without absence seizures, focal seizures, or GTCSs. GEFS+ exhibits significant genetic heterogeneity, with polymerase chain reaction, exon sequencing, and single nucleotide polymorphism analyses all showing that the occurrence of GEFS+ is mainly related to mutations in the gamma-aminobutyric acid type A receptor gamma 2 subunit (GABRG2) gene. The most common mutations in GABRG2 are separated in large autosomal dominant families, but their pathogenesis remains unclear. The predominant types of GABRG2 mutations include missense (c.983A → T, c.245G → A, p.Met199Val), nonsense (R136*, Q390*, W429*), frameshift (c.1329delC, p.Val462fs*33, p.Pro59fs*12), point (P83S), and splice site (IVS6+2T → G) mutations. All of these mutations types can reduce the function of ion channels on the cell membrane; however, the degree and mechanism underlying these dysfunctions are different and could be linked to the main mechanism of epilepsy. The γ2 subunit plays a special role in receptor trafficking and is closely related to its structural specificity. This review focused on investigating the relationship between GEFS+ and GABRG2 mutation types in recent years, discussing novel aspects deemed to be great significance for clinically accurate diagnosis, anti-epileptic treatment strategies, and new drug development.
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Affiliation(s)
- Xinxiao Li
- Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China.
| | - Shengnan Guo
- Department of Rehabilitative Medicine, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China
| | - Yangyang Sun
- Ningxia Key Laboratory of Cerebrocranial Disease, The Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, Ningxia, 750001, People's Republic of China
| | - Jiangwei Ding
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China
| | - Chao Chen
- Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China
| | - Yuehui Wu
- Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China
| | - Peidong Li
- Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China
| | - Tao Sun
- Ningxia Key Laboratory of Cerebrocranial Disease, The Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, Ningxia, 750001, People's Republic of China.
| | - Xinjun Wang
- Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China.
- Department of Neurosurgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China.
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Yu Y, Sun FJ. Research progress on the role of inflammatory mediators in the pathogenesis of epilepsy. IBRAIN 2024; 11:44-58. [PMID: 40103702 PMCID: PMC11911113 DOI: 10.1002/ibra.12162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 05/17/2024] [Accepted: 05/20/2024] [Indexed: 03/20/2025]
Abstract
Epilepsy is an abnormal neurologic disorder distinguished by the recurrent manifestation of seizures, and the precise underlying mechanisms for its development and progression remain uncertain. In recent years, the hypothesis that inflammatory mediators and corresponding pathways contribute to seizures has been supported by experimental results. The potential involvement of neuroinflammation in the development of epilepsy has garnered growing interest. This review centers attention on the involvement of inflammatory mediators in the emergence and progression of epilepsy within recent years, focusing on both clinical research and animal models, to enhance comprehension of the intricate interplay between brain inflammation and epileptogenesis.
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Affiliation(s)
- Yue Yu
- Department of Neurosurgery Affiliated Hospital of Zunyi Medical University Zunyi China
| | - Fei-Ji Sun
- Department of Neurosurgery Affiliated Hospital of Zunyi Medical University Zunyi China
- Department of Neurosurgery The First Affiliated Hospital of Chongqing Medical and pharmaceutical college Chongqing China
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Sui J, Zhan L, Ji S, Wu W, Chen Y, Yun F, Liang W, Wang J, Cao M, Shen D, Zhang Q. Differential inflammation responses determine the variable phenotypes of epilepsy induced by GABRG2 mutations. CNS Neurosci Ther 2024; 30:e14583. [PMID: 38357846 PMCID: PMC10867793 DOI: 10.1111/cns.14583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 12/11/2023] [Accepted: 12/18/2023] [Indexed: 02/16/2024] Open
Abstract
OBJECTIVE To explore the mechanism involved in variable phenotypes of epilepsy models induced by γ-aminobutyric acid type A γ2 subunit (GABRG2) mutations. METHODS The zebrafish carrying wild-type (WT) GABRG2, mutant GABRG2(P282S), GABRG2(F343L) and GABRG2(I107T) were established by Tol2kit transgenesis system and Gateway method. Behavioral analysis of different transgenic zebrafish was performed with the DanioVision Video-Track framework and the brain activity was analyzed by field potential recording with MD3000 Bio-signal Acquisition and Processing System. The transcriptome analysis was applied to detect the underlying mechanisms of variable phenotypes caused by different GABRG2 mutations. RESULTS The established Tg(hGABRG2P282S ) zebrafish showed hyperactivity and spontaneous seizures, which were more sensitive to chemical and physical epileptic stimulations. Traditional antiepileptic drugs, such as Clonazepam (CBZ) and valproic acid (VPA), could ameliorate the hyperactivity in Tg(hGABRG2P282S ) zebrafish. The metabolic pathway was significantly changed in the brain transcriptome of Tg(hGABRG2P282S ) zebrafish. In addition, the behavioral activity, production of pro-inflammatory factors, and activation of the IL-2 receptor signal pathway varied among the three mutant zebrafish lines. CONCLUSION We successfully established transgenic zebrafish epileptic models expressing human mutant GABRG2(P282S), in which CBZ and VPA showed antiepileptic effects. Differential inflammatory responses, especially the SOCS/JAK/STAT signaling pathway, might be related to the phenotypes of genetic epilepsy induced by GABRG2 mutations. Further study will expand the pathological mechanisms of genetic epilepsies and provide a theoretical basis for searching for effective drug treatment.
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Affiliation(s)
- Jiahui Sui
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of NeurologyAffiliated Hospital of Nantong University, Medical School, Co‐innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong UniversityNantongChina
| | - Longwu Zhan
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of NeurologyAffiliated Hospital of Nantong University, Medical School, Co‐innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong UniversityNantongChina
| | - Shengtao Ji
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of NeurologyAffiliated Hospital of Nantong University, Medical School, Co‐innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong UniversityNantongChina
| | - Wenwen Wu
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of NeurologyAffiliated Hospital of Nantong University, Medical School, Co‐innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong UniversityNantongChina
| | - Yuhan Chen
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of NeurologyAffiliated Hospital of Nantong University, Medical School, Co‐innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong UniversityNantongChina
| | - Feng Yun
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of NeurologyAffiliated Hospital of Nantong University, Medical School, Co‐innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong UniversityNantongChina
| | - Wenpeng Liang
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of NeurologyAffiliated Hospital of Nantong University, Medical School, Co‐innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong UniversityNantongChina
| | - Jie Wang
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of NeurologyAffiliated Hospital of Nantong University, Medical School, Co‐innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong UniversityNantongChina
| | - Maohong Cao
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of NeurologyAffiliated Hospital of Nantong University, Medical School, Co‐innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong UniversityNantongChina
| | - Dingding Shen
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of NeurologyAffiliated Hospital of Nantong University, Medical School, Co‐innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong UniversityNantongChina
| | - Qi Zhang
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of NeurologyAffiliated Hospital of Nantong University, Medical School, Co‐innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong UniversityNantongChina
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D'Amora M, Galgani A, Marchese M, Tantussi F, Faraguna U, De Angelis F, Giorgi FS. Zebrafish as an Innovative Tool for Epilepsy Modeling: State of the Art and Potential Future Directions. Int J Mol Sci 2023; 24:ijms24097702. [PMID: 37175408 PMCID: PMC10177843 DOI: 10.3390/ijms24097702] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 04/20/2023] [Accepted: 04/20/2023] [Indexed: 05/15/2023] Open
Abstract
This article discusses the potential of Zebrafish (ZF) (Danio Rerio), as a model for epilepsy research. Epilepsy is a neurological disorder affecting both children and adults, and many aspects of this disease are still poorly understood. In vivo and in vitro models derived from rodents are the most widely used for studying both epilepsy pathophysiology and novel drug treatments. However, researchers have recently obtained several valuable insights into these two fields of investigation by studying ZF. Despite the relatively simple brain structure of these animals, researchers can collect large amounts of data in a much shorter period and at lower costs compared to classical rodent models. This is particularly useful when a large number of candidate antiseizure drugs need to be screened, and ethical issues are minimized. In ZF, seizures have been induced through a variety of chemoconvulsants, primarily pentylenetetrazol (PTZ), kainic acid (KA), and pilocarpine. Furthermore, ZF can be easily genetically modified to test specific aspects of monogenic forms of human epilepsy, as well as to discover potential convulsive phenotypes in monogenic mutants. The article reports on the state-of-the-art and potential new fields of application of ZF research, including its potential role in revealing epileptogenic mechanisms, rather than merely assessing iatrogenic acute seizure modulation.
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Affiliation(s)
- Marta D'Amora
- Istituto Italiano di Tecnologia, 16163 Genova, Italy
- Department of Biology, University of Pisa, 56125 Pisa, Italy
| | - Alessandro Galgani
- Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, 56126 Pisa, Italy
| | - Maria Marchese
- Molecular Medicine and Neurobiology-ZebraLab, IRCCS Fondazione Stella Maris, 56128 Pisa, Italy
| | | | - Ugo Faraguna
- Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, 56126 Pisa, Italy
- Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris, 56128 Pisa, Italy
| | | | - Filippo Sean Giorgi
- Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, 56126 Pisa, Italy
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