Amelioration of cisplatin-induced neurodegenerative changes in rats and restoration of mitochondrial biogenesis by 6-bromoindirubin-3'-oxime: The implication of the GSK-3ß/PGC1-α axis.
Tissue Cell
; 88: 102393, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38705086
ABSTRACT
BACKGROUND:
The cognitive deficits observed after treatment with chemotherapeutic drugs are obvious clinical problems. For treating chemotherapy-induced cognitive deficits (CICD), the treatment modalities must target its underlying mechanisms. Specifically, cisplatin may activate glycogen synthase kinase-3ß (GSK-3ß), thereby enhancing neuronal apoptosis. 6-bromoindirubin-3'-oxime (6BIO) was not investigated previously in a model of CICD. Therefore, this investigation aimed to address the impacts of GSK3 inhibition on regulating cell signaling, which contributes to neurodegeneration and cognitive impairment.METHODS:
Thirty adult male Wistar rats were randomly allocated into control groups, while two experimental groups were exposed to repeated cisplatin injections (2â¯mg/kg intraperitoneally (ip), twice weekly, nine injections), termed chemobrain groups. The rats in the two experimental groups were equally divided into the chemobrain group (untreated) and the chemobrain-6BIO group (treated with 6BIO at a dose of 8.5⯵g/kg ip every two days, started after the last dose of cisplatin and continued for two weeks).RESULTS:
Repeated exposure to cisplatin led to a marked decline in cognitive functions. GSK3 inhibition exerted neuroprotection by decreasing the expression of p-tau and amyloid ß, thereby improving cognition. 6BIO, the GSK-3ß inhibitor, restored mitochondrial biogenesis by augmenting the protein levels of PGC1-α and increasing the number of mitochondria in the cerebral cortex and hippocampus.CONCLUSION:
6BIO provided neuroprotection and exhibited anti-apoptotic and anti-oxidative effects in a rat model of chemobrain.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Oximas
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Biogênese de Organelas
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Cisplatino
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Ratos Wistar
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Glicogênio Sintase Quinase 3 beta
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Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo
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Indóis
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article