Neuropharmacological and molecular characterization of Okadaic acid induced neurodegeneration in rat

Abstract

The present study is an investigation on the effect of intra cerebro ventricular (ICV) OKA on memory function in rat and associated biochemical, cellular, molecular and histological changes the brain. Due to increasing risk of chemical induced neurotoxicity and associated disorders in humans, a number of studies using pharmacological agents and natural extracts have been carried out to assess their neuroprotective potential in recent years. newlineOkadaic acid (OKA) is a selective inhibitor of the serine/threonine phosphatases 1 (PP1) and 2A (PP2A) and considered as a main culprit for memory impairment in the aged population using sea foods dinoflagellates (Helicondria Okadai) containing OKA. newline newlineThe investigation with OKA treated rat model has suggested that that OKA induces memory deficit and neurodegeneration in hippocampus and cortex along with Tau hyperphosphorylation. The major factors appear to be involved in OKA induced neurotoxicity are mitochondrial dysfunction, cholinergic dysfunction, neuroinflammation, oxidative stress and NMDA receptor. Moreover, efficacy of clinically used antidementic drugs against OKA induced changes concretes the validity of OKA induced memory impairment as an experimental model of dementia.