Ontogeny and dopaminergic regulation in brain of Ras homolog enriched in striatum (Rhes).

Ontogeny and dopaminergic regulation in brain of Ras homolog enriched in striatum (Rhes).
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DOI:
10.1016/j.brainres.2008.09.066
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发表时间:
2008-12-15
期刊:
影响因子:
2.9
通讯作者:
Ruskin DN
Ruskin DN
中科院分区:
医学3区
文献类型:
--
作者:
Harrison LM;Lahoste GJ;Ruskin DN

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Rhes 是优先在纹状体中表达的几种信号分子之一。这种 GTP 结合蛋白影响多巴胺介导的信号传导和行为。在成年期去除纹状体的多巴胺能输入神经会降低 rhes mRNA 的表达。在这里,我们发现,通过蛋白质印迹法测量,6-羟基多巴胺导致成年大鼠的多巴胺消耗导致纹状体Rhes蛋白水平显着降低。还检查了个体发育过程中多巴胺输入对 rhes mRNA 诱导的作用。在出生后第 4、6、8、10、15 和 24 天通过原位杂交测量 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 天和第 24 天逐渐增加至峰值水平。在纹状体之外,出生后海马和小脑中 rhes mRNA 高水平表达。海马信号最初在 CA3 和齿状回中最高,但到产后后期在 CA1 中表达更高。其他几个细胞核在个体发育过程中显示出低水平的 rhes mRNA。出生后第 4 天通过注射 6-羟基多巴胺消耗多巴胺不会影响 rhes mRNA 的个体发育,因此在成年期测试的病变动物与载体治疗动物中,表达没有统计学差异。这些发现表明,虽然多巴胺输入对于 rhes mRNA 表达的个体发育不是必需的,但 rhes mRNA 和 Rhes 蛋白的变化是成人纹状体对多巴胺消耗的反应的组成部分。
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.
DOI: 10.1016/0165-3806(90)90148-r
发表时间: 1990-07-01
期刊: DEVELOPMENTAL BRAIN RESEARCH
影响因子: --
作者:
EHRLICH, ME;ROSEN, NL;GREENGARD, P
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DOI: 10.1016/0165-3806(91)90157-e
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期刊: DEVELOPMENTAL BRAIN RESEARCH
影响因子: --
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发表时间: 2000-10-01
期刊: NEURON
影响因子: 16.2
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发表时间: 2000-01-01
影响因子: 1.7
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DOI: 10.1159/000017311
发表时间: 1998-03-01
影响因子: 2.9
作者:
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通讯作者: Nelson, CL