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World J Exp Med. Dec 20, 2025; 15(4): 108187
Published online Dec 20, 2025. doi: 10.5493/wjem.v15.i4.108187
Proneurogenic and microglial modulatory properties of botulinum neurotoxin in the hippocampus of aging experimental mice
Jerly Helan Mary Joseph, Mercy Priyadharshini Babu Deva Irakkam, Mahesh Kandasamy
Jerly Helan Mary Joseph, Mercy Priyadharshini Babu Deva Irakkam, Mahesh Kandasamy, Laboratory of Stem Cells and Neuroregeneration, Department of Animal Science, Bharathidasan University, Tiruchirappalli 620024, Tamil Nadu, India
Mahesh Kandasamy, University Grants Commission-Faculty Recharge Programme, New Delhi 110002, India
Author contributions: Joseph JHM contributed to formal analysis; Kandasamy M and Joseph JHM contributed to writing-original draft; Kandasamy M and Babu Deva Irakkam MP contributed to review; Joseph JHM and Babu Deva Irakkam MP contributed to methodology, acquisition of data, validation; Kandasamy M contributed to conceptualization, project administration, supervision, funding acquisition, data curation, and editing.
Supported by the Science and Engineering Research Board (SERB), No. SERB-EEQ/2016/000639; RUSA 2.0, Biological Sciences, Bharathidasan University, No. TN RUSA: 311/RUSA (2.0)/2018 dt. December 2, 2020; the University Grants Commission, Faculty Recharge Programme (UGC-FRP), New Delhi, India; Council of Scientific and Industrial Research– Senior Research Fellowship (CSIR-SRF)–Direct, No. 09/0475(23353)/2025-EMR-I.
Institutional review board statement: This work was reviewed and approved by the Institutional Animal Ethics Committee (IAEC), Bharathidasan University (Ref No: BDU/IAEC/P27/2018, August 07, 2018), under the regulation of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), India.
Institutional animal care and use committee statement: This work was reviewed and approved by the Institutional Animal Ethics Committee (IAEC), Bharathidasan University (Ref No: BDU/IAEC/P27/2018, August 07, 2018), under the regulation of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), India.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mahesh Kandasamy, PhD, UGC-Assistant Professor, Laboratory of Stem Cells and Neuroregeneration, Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620024, Tamil Nadu, India. mahesh.kandasamy@bdu.ac.in
Received: April 7, 2025
Revised: May 16, 2025
Accepted: August 4, 2025
Published online: December 20, 2025
Processing time: 256 Days and 2.3 Hours
Core Tip

Core Tip: Botulinum neurotoxin (BoNT) exerts pleiotropic effects, including notable neuroprotection. This study evaluated whether BoNT can ameliorate aging-related neuroinflammation and prevent the decline of hippocampal neurogenesis. BoNT treatment significantly reduced the number of activated microglia, accompanied by decreased expression of cyclooxygenase-2 and diminished levels of nitric oxide. Therefore, the observed increase in doublecortin-positive immature neurons and bromodeoxyuridine - neuronal nuclei double-positive newly generated neurons in the hippocampus may signify the synergistic anti-inflammatory and neuroregenerative properties of BoNT. These findings suggest that BoNT treatment could be explored as a therapeutic agent for the treatment of dementia.