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Combined use of dasatinib and quercetin alleviates overtraining-induced deficits in learning and memory through eliminating senescent cells and reducing apoptotic cells in rat hippocampus.

Authors :
Wang C
Kang Y
Liu P
Liu W
Chen W
Hayashi T
Mizuno K
Hattori S
Fujisaki H
Ikejima T
Source :
Behavioural brain research [Behav Brain Res] 2023 Feb 25; Vol. 440, pp. 114260. Date of Electronic Publication: 2022 Dec 16.
Publication Year :
2023

Abstract

Excessive physical exercise (overtraining, OT) charactered by long-term and excessive training results in the damage of multiple vital tissues including hippocampus which plays a critical role in learning and memory. A combination of dasatinib (D) plus quercetin (Q) (D+Q) belongs to senolytic drugs which selectively kill senescent cells in vitro and vivo. In this study, the rats that suffered a five-week excessive swimming training were subjected to the oral administration of D+Q. D+Q alleviated the decline in exercise performance of OT rats during the swimming training, and prevented learning and memory deficits in Morris water maze, Y-maze and novel object recognition tests after excessive swimming training. Analytical results by SA-β-gal staining and western blotting showed that D+Q significantly reduced senescent cells with repressed expression of senescence-related proteins, p53 and p21, in hippocampus. Nissl and immunohistochemical staining showed that D+Q significantly attenuated neuronal loss caused by apoptosis. Interestingly, we observed elevated level of cleaved caspase 3, an apoptosis executor protein, in p21 positive hippocampus cells by D+Q treatment in immunofluorescent staining, suggesting that senescent cells were induced to apoptosis in D+Q-treated rats. The positive control drug, silibinin, showed similar protective effect against OT, but did not induce the apoptosis of senescent cells, suggesting a difference in the protective mechanisms. These results indicated that D+Q alleviates overtraining-induced deficits in learning and memory through elimination of senescent cells and reduction of apoptotic cell number.<br />Competing Interests: Declarations of interest None.<br /> (Copyright © 2022. Published by Elsevier B.V.)

Details

Language :
English
ISSN :
1872-7549
Volume :
440
Database :
MEDLINE
Journal :
Behavioural brain research
Publication Type :
Academic Journal
Accession number :
36535433
Full Text :
https://doi.org/10.1016/j.bbr.2022.114260