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Amelioration of cisplatin-induced neurodegenerative changes in rats and restoration of mitochondrial biogenesis by 6-bromoindirubin-3′-oxime: The implication of the GSK-3β/PGC1-α axis.
- Source :
- Tissue & Cell; Jun2024, Vol. 88, pN.PAG-N.PAG, 1p
- Publication Year :
- 2024
-
Abstract
- 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-3β (GSK-3β), 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. Thirty adult male Wistar rats were randomly allocated into control groups, while two experimental groups were exposed to repeated cisplatin injections (2 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 μg/kg ip every two days, started after the last dose of cisplatin and continued for two weeks). 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 β, thereby improving cognition. 6BIO, the GSK-3β inhibitor, restored mitochondrial biogenesis by augmenting the protein levels of PGC1-α and increasing the number of mitochondria in the cerebral cortex and hippocampus. 6BIO provided neuroprotection and exhibited anti-apoptotic and anti-oxidative effects in a rat model of chemobrain. • The treatment modalities of chemotherapy-induced cognitive deficits (CICD) must target its underlying mechanisms. • The potent inhibitor of GSK-3β, 6BIO, has shown anti-neurodegenerative activities. • 6BIO reduced the oxidative load and promoted the activation of antioxidant mechanisms. • The inhibition of GSK3-β was associated with enhanced expression of PGC1-α and Bcl-2 in brain tissues. [ABSTRACT FROM AUTHOR]
- Subjects :
- LABORATORY rats
RATS
MITOCHONDRIA
CEREBRAL cortex
CISPLATIN
CHEMORECEPTORS
Subjects
Details
- Language :
- English
- ISSN :
- 00408166
- Volume :
- 88
- Database :
- Supplemental Index
- Journal :
- Tissue & Cell
- Publication Type :
- Academic Journal
- Accession number :
- 177858871
- Full Text :
- https://doi.org/10.1016/j.tice.2024.102393