Loss of MeCP2 in aminergic neurons causes cell-autonomous defects in neurotransmitter synthesis and specific behavioral abnormalities
Loss of MeCP2 in aminergic neurons causes cell-autonomous defects in neurotransmitter synthesis and specific behavioral abnormalities
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DOI：
10.1073/pnas.0912257106
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发表时间：
2009-12-22
影响因子：
11.1
通讯作者：
Neul, Jeffrey L.
中科院分区：
文献类型：
--
作者：
Samaco, Rodney C.;Mandel-Brehm, Caleigh;Neul, Jeffrey L.
Rett综合征（RTT）的特征是特定的运动、认知和行为缺陷。由于这些异常中的一些发生在与胺能神经递质改变相关的其他疾病状态中，我们研究了这种改变对RTT发病机制的贡献。我们发现RTT和Mecp2缺失小鼠的个体都具有低于正常水平的胺能代谢物和含量。从TH阳性多巴胺能和去甲肾上腺素能神经元或PET1阳性多巴胺能神经元中删除Mecp2可能会降低相应的神经递质浓度和特定表型，这可能是通过MeCP2调节参与胺能神经递质产生的限速酶。这些数据支持细胞自主的，MeCP2依赖性的机制，用于调节胺能神经递质的合成，有助于独特的行为表型。
Rett syndrome (RTT) is characterized by specific motor, cognitive, and behavioral deficits. Because several of these abnormalities occur in other disease states associated with alterations in aminergic neurotransmitters, we investigated the contribution of such alterations to RTT pathogenesis. We found that both individuals with RTT and Mecp2-null mice have lower-than-normal levels of aminergic metabolites and content. Deleting Mecp2 from either TH-positive dopaminergic and noradrenergic neurons or PET1-positive serotonergic neurons in mice decreased corresponding neurotransmitter concentration and specific phenotypes, likely through MeCP2 regulation of rate-limiting enzymes involved in aminergic neurotransmitter production. These data support a cell-autonomous, MeCP2-dependent mechanism for the regulation of aminergic neurotransmitter synthesis contributing to unique behavioral phenotypes.