Human COMT over-expression confers a heightened susceptibility to dyskinesia in mice.
Human COMT over-expression confers a heightened susceptibility to dyskinesia in mice.
复制标题
人类 COMT 过度表达导致小鼠对运动障碍的易感性增加。
DOI：
10.1016/j.nbd.2017.03.006
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发表时间：
2017
影响因子：
6.1
通讯作者：
Moratalla,Rosario
中科院分区：
文献类型：
--
作者：
Solís,Oscar;García-Montes,Jose-Rubén;Garcia-Sanz,Patricia;Herranz,AntonioS;Asensio,Maria-José;Kang,Gina;Hiroi,Noboru;Moratalla,Rosario
Catechol-O-methyltransferase (COMT) degrades dopamine and its precursorl-DOPA and plays a critical role in regulating synaptic dopamine actions. We investigated the effects of heightened levels of COMT on dopamine-regulated motor behaviors and molecular alterations in a mouse model of dyskinesia. Transgenic mice overexpressing human COMT (TG) and their wildtype (WT) littermates received unilateral 6-OHDA lesions in the dorsal striatum and were treated chronically withl-DOPA for two weeks.l-DOPA-induced dyskinesia was exacerbated in TG mice without alteringl-DOPA motor efficacy as determined by contralateral rotations or motor coordination. Inductions of FosB and phospho-acetylated histone 3 (molecular correlates of dyskinesia) were potentiated in the lesioned striatum of TG mice compared with their WT littermates. The TG mice had lower basal levels of dopamine in the striatum. In mice with lesions,l-DOPA induces a greater increase in the dopamine metabolite 3-methoxytyramine in the lesioned striatum of dyskinetic TG mice than in WT mice. The levels of serotonin and its metabolite were similar in TG and WT mice. Our results demonstrate that human COMT overexpression confers a heightened susceptibility tol-DOPA-induced dyskinesia and alters molecular and neurochemical responses in the lesioned striatum of mice.
