02781nas a2200313   4500008004100000022001400041245018000055210006900235260000900304300001100313490000900324520172200333653002402055653001902079653000902098653001102107653002102118653001802139100002102157700002102178700001602199700002702215700002402242700001002266700002502276700001902301700001902320856012802339       2021                        eng d  a0006-899300aProtriptyline improves spatial memory and reduces oxidative damage by regulating NF kappa B-BDNF/CREB signaling axis in streptozotocin-induced rat model of Alzheimer's disease0 aProtriptyline improves spatial memory and reduces oxidative dama  cMAR   a1472610 v17543 a<p>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 mu l 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, A beta 42 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 WO and reduced CREB and BDNF expression in cortex and hippocampus. Interestingly, PRT treatment significantly reduced pTau, A beta 42 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 NFXB and GFAP expression in STZ treated rats. Our data suggest that impaired NFXB 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.</p>
10aAlzheimer's disease10aantidepressant10aBDNF10aMemory10aOxidative stress10aProtriptyline1 aTiwari, Virendra1 aMishra, Akanksha1 aSingh, Sonu1 aMishra, Sandeep, Kumar1 aSahu, Kiran, Kumari1 aParul1 aKulkarni, Mahesh, J.1 aShukla, Rakesh1 aShukla, Shubha  uhttps://library.ncl.res.in/content/protriptyline-improves-spatial-memory-and-reduces-oxidative-damage-regulating-nf-kappa-b