کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8837668 | 1612884 | 2018 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Fasudil hydrochloride ameliorates memory deficits in rat model of streptozotocin-induced Alzheimer's disease: Involvement of PI3-kinase, eNOS and NFκB
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
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چکیده انگلیسی
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 (300â¯Î¼g/kg, ICV) averted the STZ-ICV (3â¯mg/kg) induced memory dysfunctions in rats. Wortmannin (5â¯Î¼g/rat) or l-NAME (20â¯mg/kg) attenuated the memory restorative function of fasudil in STZ treated rats. However, l-Arginine (50â¯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 cholinergic activities of fasudil. Although brain nitrite content was decreased by l-NAME and wortmannin, the l-NAME group depicted rise in eNOS content (not activity) and NFκB expression, whereas, decrease in same was observed in wortmannin group. l-Arginine lowered the brain oxidative stress, inflammation, AChE activity, eNOS expression (not activity), NFκB levels and elevated nitrite content. In STZ-ICV rat model of AD, fasudil (Rho-kinase inhibitor) ameliorated the AD symptoms by reinstating PI3-kinase mediated upregulation of eNOS and control over brain NFκB activity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Behavioural Brain Research - Volume 351, 1 October 2018, Pages 4-16
Journal: Behavioural Brain Research - Volume 351, 1 October 2018, Pages 4-16
نویسندگان
Manish Kumar, Nitin Bansal,