EFFECT OF MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR IN ANIMAL MODEL OF ALZHEIMER’S DISEASES

Abstract

Stress activated protein kinases such as p38 MAPK have been implicated in the pathogenesis of Alzheimer’s disease (AD). The present study was designed to investigate the effect of SB203580 – a p38 MAPK inhibitor-in intracerebroventricular-streptozotocin (i.c.v - STZ) induced cognitive deficits and oxidative-nitritive stress. i.c.v.-STZ, injected twice (3mg/kg) 48h apart, resulted in significant impairment of learning and memory, cholinergic hypofunction and increased oxidative-nitritive stress. Sub-chronic treatment of SB203580 at different doses (0.25, 5 & 1 μg/5μl/ventricle) from day 4 to day 21 following first i.c.v - STZ injection, significantly improved learning and memory in Morris water maze task. Furthermore, SB203580 significantly reduced the oxidative-nitritive stress as evidenced by decrease in malondialdehyde (MDA) and nitrite levels and increased glutathione (GSH) levels. In addition elevation in acetylcholinesterase (AChE) activity following i.c.v.-STZ on day 22 was significantly reduced by SB203580. Results of the present study have thus demonstrated the facilitatory role of p38 MAPK in cognitive deficit, cholinergic hypofunction and increase in oxidative-nitritive stress following i.c.v.-STZ and favour the potential of p38 MAPK inhibition in neurodegenerative disorders associated with oxidative and cognitive dysfunction