Protective effect of metformin on methotrexate induced reduction of rat hippocampal neural stem cells and neurogenesis.

Autor: Sritawan N; Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Neurogenesis Research Group, Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: natasr@kku.ac.th., Sirichoat A; Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Neurogenesis Research Group, Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: apiwsi@kku.ac.th., Aranarochana A; Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Neurogenesis Research Group, Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: anusar@kku.ac.th., Pannangrong W; Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Neurogenesis Research Group, Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: wankun@kku.ac.th., Wigmore P; School of Life Sciences, Medical School, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2RD, UK. Electronic address: peter.wigmore@nottingham.ac.uk., Welbat JU; Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Neurogenesis Research Group, Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: jariya@kku.ac.th.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2023 Jun; Vol. 162, pp. 114613. Date of Electronic Publication: 2023 Mar 29.
DOI: 10.1016/j.biopha.2023.114613
Abstrakt: Adult neurogenesis is a process in which the adult neural stem cells produce newborn neurons that are implicated in terms of learning and memory. Methotrexate (MTX) is a chemotherapeutic drug, which has a negative effect on memory and hippocampal neurogenesis in animal models. Metformin is an antidiabetic drug with strong antioxidant capacities. We found that metformin ameliorates MTX induced deteriorations of memory and hippocampal neurogenesis in adult rats. In this study, we focus to investigate neural stem cells, biomarkers of apoptosis, and the protein for synaptogenesis, which involves in the transcription factors of the hippocampus in rats that received metformin and MTX. Male Sprague-Dawley rats were composed of control, MTX, metformin, and MTX+metformin groups. MTX (75 mg/kg, i.v.) was given on days 7 and 14, whereas metformin (200 mg/kg, i.p.) was given for 14 days. Hippocampal neural stem cells in the subgranular zone (SGZ) were quantified using immunofluorescence staining of Sox2 and nestin. Protein expression including PSD95, Casepase-3, Bax, Bcl-2, CREB, and pCREB were determined using Western blotting. MTX-treated rats displayed decreases in Sox2 and nestin-positive cells in the SGZ. Increases in Caspase-3 and Bax levels and decreases in PSD95, Bcl-2, CREB, and pCREB protein expressions in the hippocampus were also detected. However, these negative impacts of MTX were ameliorated by co-treatment with metformin. These consequences postulate that metformin has a potential to increase neural stem cells, synaptic plasticity, decreased apoptotic activities, and transcription factors, resulting in upregulation of hippocampal neurogenesis in MTX-treated rats.
Competing Interests: Conflict of Interest Statement The authors declare that there are no conflicts of interest.
(Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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