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- W3121036994 endingPage "147261" @default.
- W3121036994 startingPage "147261" @default.
- W3121036994 abstract "Antidepressants are well known to exert their role via upregulation of brain derived neurotrophic factor (BDNF). BDNF has been reported to exerts its neuroprotective effect in rodent and primate models as well as in patients of Alzheimer's disease (AD). The aim of our study was to evaluate the effect of protriptyline (PRT), a tricyclic antidepressant, in streptozotocin (STZ)- induced rat model of AD. Total 10 µl of STZ was injected into each ventricle (1 mg/kg). PRT (10 mg/kg, i.p.) treatment was started 3-day post STZ administration and continued till 21 days. We found that STZ treatment significantly increased pTau, Aβ42 and BACE-1 expression, oxidative stress and neurodegeneration in hippocampus and cortex of adult rats. STZ induced impairment in spatial learning and retention memory was associated with increased NFκB and reduced CREB and BDNF expression in cortex and hippocampus. Interestingly, PRT treatment significantly reduced pTau, Aβ42 and BACE-1 levels, neurodegeneration, oxidative stress and glial activation, contributing to the improved spatial learning and retention memory in STZ treated rats. Moreover, PRT treatment significantly improved p-ERK/ERK ratio and enhanced BDNF and CREB levels by reducing NFκB and GFAP expression in STZ treated rats. Our data suggest that impaired NFκB and CREB signaling potentially contribute in AD pathogenesis by elevating oxidative stress and neuroinflammation mediated neurodegeneration. Our study has established protriptyline as a multi target molecule in pre-clinical model of AD and further investigations on PRT like molecules could pave way for further development of effective new treatments in neurodegenerative disorders." @default.
- W3121036994 created "2021-01-18" @default.
- W3121036994 creator A5005548875 @default.
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- W3121036994 creator A5085854353 @default.
- W3121036994 date "2021-03-01" @default.
- W3121036994 modified "2023-09-30" @default.
- W3121036994 title "Protriptyline improves spatial memory and reduces oxidative damage by regulating NFκB-BDNF/CREB signaling axis in streptozotocin-induced rat model of Alzheimer’s disease" @default.
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