Haloperidol protects striatal neurons from dysfunction induced by mutated huntingtin in vivo.

Details

Serval ID
serval:BIB_CDFEFDD93FE1
Type
Article: article from journal or magazin.
Collection
Publications
Title
Haloperidol protects striatal neurons from dysfunction induced by mutated huntingtin in vivo.
Journal
Neurobiology of Disease
Author(s)
Charvin D., Roze E., Perrin V., Deyts C., Betuing S., Pagès C., Régulier E., Luthi-Carter R., Brouillet E., Déglon N., Caboche J.
ISSN
0969-9961 (Print)
ISSN-L
0969-9961
Publication state
Published
Issued date
2008
Volume
29
Number
1
Pages
22-29
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
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 vivo 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.
Keywords
Age Factors, Animals, Antipsychotic Agents/therapeutic use, Cell Count/methods, Corpus Striatum/metabolism, Corpus Striatum/pathology, Disease Models, Animal, Dopamine and cAMP-Regulated Phosphoprotein 32/metabolism, Female, Gene Expression Regulation/drug effects, Haloperidol/analogs & derivatives, Haloperidol/therapeutic use, Huntington Disease/genetics, Huntington Disease/pathology, Lentivirus/physiology, Mutation/physiology, Nerve Tissue Proteins/genetics, Neurons/drug effects, Nuclear Proteins/genetics, Phosphopyruvate Hydratase/metabolism, Rats, Rats, Wistar
Pubmed
Web of science
Create date
13/12/2011 17:18
Last modification date
20/08/2019 16:48
Usage data