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Loss of MeCP2 in aminergic neurons causes cell-autonomous defects in neurotransmitter synthesis and specific behavioral abnormalities.

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.

SUBMITTER: Samaco RC 

PROVIDER: S-EPMC2799790 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Loss of MeCP2 in aminergic neurons causes cell-autonomous defects in neurotransmitter synthesis and specific behavioral abnormalities.

Samaco Rodney C RC   Mandel-Brehm Caleigh C   Chao Hsiao-Tuan HT   Ward Christopher S CS   Fyffe-Maricich Sharyl L SL   Ren Jun J   Hyland Keith K   Thaller Christina C   Maricich Stephen M SM   Humphreys Peter P   Greer John J JJ   Percy Alan A   Glaze Daniel G DG   Zoghbi Huda Y HY   Neul Jeffrey L JL  

Proceedings of the National Academy of Sciences of the United States of America 20091209 51

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  ...[more]

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