Fasudil hydrochloride ameliorates memory deficits in rat model of streptozotocin-induced Alzheimer's disease: Involvement of PI3-kinase, eNOS and NF κB.

Fasudil hydrochloride ameliorates memory deficits in rat model of streptozotocin-induced Alzheimer's disease: Involvement of PI3-kinase, eNOS and NFκB.
Behav Brain Res. 2018 May 25;:
Authors: Kumar M, Bansal N
Abstract
Restoration of PI3-kinase signaling portrays therapeutic potential in Alzheimer's disease (AD). Hyperactive Rho-kinase in AD negatively modulates PI3-kinase pathway, thereby cause cognitive decline. Fasudil is a Rho-kinase inhibitor that has shown therapeutic benefits in brain disorders. The present study is aimed to decipher the role of PI3-kinase pathway in neuroprotective activity of fasudil using STZ-ICV model of AD. MWM and NORT showed that fasudil (300 µg/kg, ICV) averted the STZ-ICV (3 mg/kg) induced memory dysfunctions in rats. Wortmannin (5 µg/rat) or L-NAME (20 mg/kg) attenuated the memory restorative function of fasudil in STZ treated rats. However, L-Arginine (50 mg/kg) group exhibited marked improvement in memory functions. Markers of oxidative stress (TBARS, GSH, SOD, CAT), nitrite, AChE, TNF-α, eNOS and NFκB were measured in whole brain of rats. STZ-ICV group exhibited significant elevation in brain oxidative stress, AChE activity, TNF-α, NFκB expression and decrease in eNOS level. These effects of STZ were effectively ameliorated by administration of fasudil for 21 days. Wortmannin (PI3-kinase inhibitor) or L-NAME (NOS blocker) attenuated the antioxidative, anti-inflammatory and choline...

Source: Behavioural Brain Research - May 25, 2018 Category: Neurology Authors: Kumar M, Bansal N Tags: Behav Brain Res Source Type: research