在单胺能神经元中缺失 MeCP2 会导致神经递质合成的自主细胞缺陷和特定的行为异常。
Loss of MeCP2 in aminergic neurons causes cell-autonomous defects in neurotransmitter synthesis and specific behavioral abnormalities.
机构信息
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
出版信息
Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21966-71. doi: 10.1073/pnas.0912257106. Epub 2009 Dec 9.
Abstract
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.
摘要
雷特综合征（RTT）的特征是特定的运动、认知和行为缺陷。由于这些异常中的许多存在于与氨基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，患有 RTT 的个体和 Mecp2 基因敲除小鼠都存在低于正常水平的氨基能代谢物和含量。在小鼠中从 TH 阳性多巴胺能和去甲肾上腺素能神经元或 PET1 阳性 5-羟色胺能神经元中删除 Mecp2 会降低相应的神经递质浓度和特定表型，这可能是通过 MeCP2 调节参与氨基能神经递质产生的限速酶。这些数据支持氨基能神经递质合成的细胞自主、MeCP2 依赖性调节机制，该机制有助于独特的行为表型。
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