altered dopamine and serotonin metabolism in motorically asymptomatic r62 mice多巴胺和血清素代谢改变动作无症状r62老鼠.pdfVIP

Altered Dopamine and Serotonin Metabolism in Motorically Asymptomatic R6/2 Mice 1,2,3,4 4 1,2 4 Fanny Mochel *, Brandon Durant , Alexandra Durr , Raphael Schiffmann ˆ ˆ ` ´ ´ ´ ˆ ˆ ` 1 INSERM UMR S975, Institut du Cerveau et de la Moelle, Hopital de La Salpetriere, Paris, France, 2 AP-HP, Departement de Genetique, Hopital de La Salpetriere, Paris, ´ France, 3 Universite Pierre et Marie Curie, Paris, France, 4 Institute of Metabolic Disease, Baylor Research Institute, Dallas, Texas, United States of America Abstract The pattern of cerebral dopamine (DA) abnormalities in Huntington disease (HD) is complex, as reflected by the variable clinical benefit of both DA antagonists and agonists in treating HD symptoms. In addition, little is known about serotonin metabolism despite the early occurrence of anxiety and depression in HD. Post-mortem enzymatic changes are likely to interfere with the in vivo profile of biogenic amines. Hence, in order to reliably characterize the regional and chronological profile of brain neurotransmitters in a HD mouse model, we used a microwave fixation system that preserves in vivo concentrations of dopaminergic and serotoninergic amines. DA was decreased in the striatum of R6/2 mice at 8 and 12 weeks of age while DA metabolites, 3-methoxytyramine and homovanillic acid, were already significantly reduced in 4- week-old motorically asymptomatic R6/2 mice. In the striatum, hippocampus and frontal cortex of 4, 8 and 12-week-old R6/ 2 mice, serotonin and its metabolite 5-hydroxyindoleacetic acid were significantly decreas