P2–009: Melatonin ameliorated calyculin A–induced hyperphosphorylation of neurofilaments and spatial memory deficit in rats

Much evidence has shown a reduction of activities of protein phosphatase 2A (PP–2A) and PP–1 leads to tau hyperphosphorylation, a main component of neurofibrillary tangles. Evidence indicates that cytoskeleton protein neurofilament as well as tau is also involved in the pathogenesis of Alzheimer's disease(AD). In AD patient brains, hyperphosphorylation and accumulation of neurofilament proteins has been found, however, the underlying mechanism resulting in hyperphosphorylation and abnormal accumulation of neurofilament is not well understood. To investigate whether the reduced acitivities of PP–2A/PP–1 induce Alzheimer–like hyperphosphorylation and accumulation of neurofilament proteins in vivo or not and find an effective cure for arresting neurofilament hyperphosphorylation. Western Blot; Immunohistochemistry; Morris Water Maze and Hippocampus Injection. (i) PP–2A and PP–1 participate in the in vivo regulation of neurofilament phosphorylation, and reduced activities of PP–2A/PP–1 will result in neurofilament hyperphosphorylation; (ii) neurofilament hyperphosphorylation might be crucial to affect spatial memory in AD; (iii) melatonin might be an effective therapeutic agent for AD by depressing neurofilament hyperphosphorylation and improving memory retention.