VALPROIC ACID ENHANCES MICROGLIAL PHAGOCYTOSIS OF AMYLOID-β1-42

Alzheimer's disease (AD) is a prevalent neurode-generative disorder manifested by memory loss, confusion and changes in mood. A principal pathology of this debilitating disorder is extracellular deposits of amyloid-beta (A beta) protein. The "amyloid hypothesis" postulates that a build-up of A beta protein is responsible for neuronal loss and the ensuing symptoms of AD. One possible mechanism of A beta clearance, and hence AD therapy, is phagocytosis of A beta protein by microglial cells. Microglia are the brain's resident immune cells and phagocytosis is one of their innate functions. We are interested in identifying molecules that augment microglial-mediated phagocytosis of A beta protein. We used the rodent BV-2 microglial cell line which readily phagocytose fluorescent latex beads and synthetic A beta(1-42) peptide. BV-2 cells treated with the neuroactive drug valproic acid (VPA) showed greatly enhanced phagocytic activity for both latex beads and A beta. VPA also reduced microglial viability by inducing apoptosis, as previously reported. The relevance of these in vitro results to the treatment of AD is unclear but further investigation into the effects of VPA on the clearance of A beta through enhanced microglial phagocytosis is warranted. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.