title: Haloperidol protects striatal neurons from dysfunction induced by mutated huntingtin in vivo.
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.
authors: Signalisation Neuronale et Régulations Géniques, Centre National de la Recherche Scientifique, Université Pierre et Marie Curie, UMR 7102, 9 quai Saint Bernard, 75005 Paris, France.
authors: Delphine
authors: D
authors: Charvin
authors: Emmanuel
authors: E
authors: Roze
authors: Valérie
authors: V
authors: Perrin
authors: Carole
authors: C
authors: Deyts
authors: Sandrine
authors: S
authors: Betuing
authors: Christiane
authors: C
authors: Pagès
authors: Etienne
authors: E
authors: Régulier
authors: Ruth
authors: R
authors: Luthi-Carter
authors: Emmanuel
authors: E
authors: Brouillet
authors: Nicole
authors: N
authors: Déglon
authors: Jocelyne
authors: J
authors: Caboche
mesh_terms: D000367:Age Factors; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002452:Cell Count / Q000379:methods; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D016086:Lentivirus / Q000502:physiology; D009154:Mutation / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000187:drug effects*; D009687:Nuclear Proteins / Q000235:genetics*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D014150:Antipsychotic Agents; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C497930:Ppp1r1b protein, rat; C033563:haloperidol decanoate; D010751:Phosphopyruvate Hydratase; D006220:Haloperidol