Haloperidol protects striatal neurons from dysfunction induced by mutated huntingtin in vivo
Huntington's disease (HD) results from an abnormal polyglutamine extension in the N-terminal region of the huntingtin protein. This mutation causes preferential degeneration of striatal projection neurons. We previously demonstrated, in vitro, that dopaminergic D2 receptor stimulation acted synergistically with mutated huntingtin (expHtt) to increase aggregate formation and striatal death. In the present work, we extend these observations to an in viva system based on lentiviral-mediated expression of expHtt in the rat striatum. The early and chronic treatment with the D2 antagonist haloperidol decanoate protects striatal neurons from expHtt-induced dysfunction, as analyzed by DARPP-32 and NeuN stainings. Haloperidol treatment also reduces aggregates formation, an effect that is maintained over time. These findings indicate that D2 receptors activation contributes to the deleterious effects of expHtt on striatal function and may represent an interesting early target to alter the subsequent course of neuropathology in HD. (c) 2007 Elsevier Inc. All rights reserved.
Keywords: dopamine ; D2 receptor ; lentiviral infection ; Huntington's disease ; polyQ huntingtin ; NeuN ; Darpp-32 ; striatal dysfunction ; Disease Transgenic Mice ; Basal Ganglia Volume ; Mouse Model ; Mutant Huntingtin ; Intranuclear Inclusions ; Expanded Huntingtin ; Glucose-Metabolism ; Motor Dysfunction ; Messenger-Rna ; Rat Striatum
Record created on 2010-11-30, modified on 2016-08-09