Harrison Laura M, Lahoste Gerald J, Ruskin David N
Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans, LA 70112, USA.
Brain Res. 2008 Dec 15;1245:16-25. doi: 10.1016/j.brainres.2008.09.066. Epub 2008 Oct 2.
Rhes is one of several signaling molecules preferentially expressed in the striatum. This GTP-binding protein affects dopamine-mediated signaling and behavior. Denervating the striatum of its dopaminergic inputs in adulthood reduces rhes mRNA expression. Here we show that dopamine depletion in adult rats by 6-hydroxydopamine caused a significant decrease in striatal Rhes protein levels as measured by Western blotting. The role of dopamine input on rhes mRNA induction during ontogeny was also examined. Rhes mRNA was measured on postnatal days 4, 6, 8, 10, 15, and 24 with in situ hybridization to determine its normal ontogeny. Signal in striatum was detectable, but very low, on postnatal day 4 and increased gradually to peak levels at days 15 and 24. Outside of the striatum, rhes mRNA was expressed at high levels in hippocampus and cerebellum during the postnatal period. Hippocampal signal was initially highest in CA3 and dentate gyrus, but shifted to higher expression in CA1 by the late postnatal period. Several other nuclei showed low levels of rhes mRNA during ontogeny. Depletion of dopamine by 6-hydroxydopamine injection on postnatal day 4 did not affect the ontogenetic development of rhes mRNA, such that expression did not differ statistically in lesioned versus vehicle-treated animals tested in adulthood. These findings suggest that although dopamine input is not necessary for the ontogenetic development of rhes mRNA expression, changes in both rhes mRNA and Rhes protein are integral components of the response of the adult striatum to dopamine depletion.
Rhes是几种在纹状体中优先表达的信号分子之一。这种GTP结合蛋白影响多巴胺介导的信号传导和行为。成年期去除纹状体的多巴胺能输入会降低Rhes mRNA的表达。在这里，我们表明，通过6-羟基多巴胺使成年大鼠多巴胺耗竭，通过蛋白质印迹法检测发现纹状体Rhes蛋白水平显著降低。我们还研究了多巴胺输入在个体发育过程中对rhes mRNA诱导的作用。通过原位杂交在出生后第4、6、8、10、15和24天测量Rhes mRNA，以确定其正常个体发育。出生后第4天，纹状体中的信号可检测到，但非常低，并在第15天和24天逐渐增加至峰值水平。在纹状体之外，出生后海马体和小脑中rhes mRNA高水平表达。海马体信号最初在CA3和齿状回中最高，但在出生后期转移到CA1中更高的表达。其他几个核在个体发育过程中rhes mRNA水平较低。在出生后第4天注射6-羟基多巴胺使多巴胺耗竭，并不影响rhes mRNA的个体发育，因此在成年期测试的损伤动物与接受载体处理的动物中，其表达在统计学上没有差异。这些发现表明，尽管多巴胺输入对于rhes mRNA表达的个体发育不是必需的，但rhes mRNA和Rhes蛋白的变化都是成年纹状体对多巴胺耗竭反应的组成部分。
