dopamine d2 receptor stimulation potentiates polyq-huntingtin-induced mouse striatal neuron dysfunctions via rhorock-ii activation多巴胺d2受体刺激强化polyq-huntingtin-induced鼠标通过rhorock-ii激活纹状体神经元的障碍.pdfVIP

Dopamine D2 Receptor Stimulation Potentiates PolyQ- Huntingtin-Induced Mouse Striatal Neuron Dysfunctions via Rho/ROCK-II Activation Carole Deyts1,2,3, Beatriz Galan-Rodriguez1,2, Elodie Martin1,2, Nicolas Bouveyron1,2, Emmanuel 1,2,4 1,2 1,2. ´ 1,2,5. Roze , Delphine Charvin , Jocelyne Caboche , Sandrine Betuing * ´ ´ 1 CNRS UMR 7102, Universite Pierre et Marie Curie-Paris 6, Paris, France, 2 INSERM UMRS 952, CNRS UMR 7224, Universite Pierre et Marie Curie-Paris 6, Paris, France, ˆ ˆ ` ˆ 3 Biological Sciences Division, University of Chicago, Chicago, Illinois, United States of America, 4 Service de Neurologie, Hopital Salpetriere, Assitance Publique-Hopitaux ´ de Paris, Paris, France, 5 Universite Evry Val d’Essonne, Evry, France Abstract Background: Huntington’s disease (HD) is a polyglutamine-expanded related neurodegenerative disease. Despite the ubiquitous expression of expanded, polyQ-Huntingtin (ExpHtt) in the brain, striatal neurons present a higher susceptibility to the mutation. A commonly admitted hypothesis is that Dopaminergic inputs participate to this vulnerability. We previously showed that D2 receptor stimulation increased aggregate formation and neuronal death induced by ExpHtt in primary striatal neurons in culture, and chronic D2 antagonist treatment protects striatal dysfunctions induced by ExpHtt in a lentiviral-induced model s