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

by Samaco, Rodney C , Mandel-Brehm, Caleigh , Thaller, Christina , Zoghbi, Huda Y , Chao, Hsiao-Tuan , Hyland, Keith , Ward, Christopher S , Maricich, Stephen M , Ren, Jun , Percy, Alan , Fyffe-Maricich, Sharyl L , Glaze, Daniel G , Humphreys, Peter , Greer, John J , Neul, Jeffrey L

in Amines - metabolism / Animals / Biological Sciences / Breathing / Cells / cognition / Cognition & reasoning / Enzymes / Genetic mutation / Genotype & phenotype / Homovanillic Acid - metabolism / Hydroxyindoleacetic Acid - metabolism / Intellectual disability / Mental Disorders - metabolism / Metabolites / Methyl-CpG-Binding Protein 2 - genetics / Methyl-CpG-Binding Protein 2 - metabolism / Mice / Mice, Knockout / Neurons / Neurons - enzymology / Neurons - metabolism / Neurotransmitters / Norepinephrine / pathogenesis / Phenotype / Phenotypes / Rodents / Tryptophan Hydroxylase - metabolism / Tyrosine 3-Monooxygenase - metabolism

2009

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

2009

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

2009

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Journal Article

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

Samaco, Rodney C,

Mandel-Brehm, Caleigh,

Thaller, Christina,

Zoghbi, Huda Y,

Chao, Hsiao-Tuan,

Hyland, Keith,

Ward, Christopher S,

Maricich, Stephen M,

Ren, Jun,

Percy, Alan,

Fyffe-Maricich, Sharyl L,

Glaze, Daniel G,

Humphreys, Peter,

Greer, John J,

Neul, Jeffrey L

2009

Overview

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.

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Publisher

National Academy of Sciences,National Acad Sciences

Subject

Amines - metabolism

/ Animals

/ Biological Sciences

/ Breathing

/ Cells

/ cognition

/ Cognition & reasoning