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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.
- Source :
-
Behavioural Brain Research . Feb2023, Vol. 440, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
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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. [Display omitted] • Dasatinib + quercetin treatment prevents OT-induced learning and memory deficits. • Dasatinib + quercetin induces apoptosis of senescent cells in hippocampus. • Dasatinib + quercetin alleviates apoptotic neuronal loss in hippocampus. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01664328
- Volume :
- 440
- Database :
- Academic Search Index
- Journal :
- Behavioural Brain Research
- Publication Type :
- Academic Journal
- Accession number :
- 161172214
- Full Text :
- https://doi.org/10.1016/j.bbr.2022.114260