Anxiolytic agent, dihydrohonokiol-B, recovers amyloid beta protein-induced neurotoxicity in cultured rat hippocampal neurons

Abstract

The effects of anxiolytic honokiol derivative, dihydrohonokiol-B (DHH-B), on amyloid beta protein (Abeta(25-35), 10 nM)-induced changes in Cl(-)-ATPase activity, intracellular Cl- concentration ([Cl-]i) and glutamate neurotoxicity were examined in cultured rat hippocampal neurons. DHH-B (10 ng/ml) recovered Abeta-induced decrease in neuronal Cl(-)-ATPase activity without any changes in the activities of Na+/K+-ATPase and anion-insensitive Mg2+-ATPase. A GABA(C) receptor antagonist (1,2,5,6,-tetrahydropyridin-4-yl) methyl-phosphinic acid (TPMPA, 15 microM), inhibited the protective effects of DHH-B on Cl(-)-ATPase activity. DHH-B reduced Abeta-induced elevation of [Cl-]i as assayed using a Cl(-)-sensitive fluorescent dye, and prevented Abeta-induced aggravation of glutamate neurotoxicity. These data suggest that DHH-B exerts the neuroprotective action against Abeta through GABA(C) receptor stimulation.