Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 51, Pages 21966-21971Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0912257106
Keywords
dopamine; norepinephrine; Rett syndrome; serotonin
Categories
Funding
- Autism Speaks
- National Institutes of Health [NS057819, HD024064, NS052240, MH078678]
- International Rett Syndrome Foundation
- Simons Foundation
- Huda Zoghbi is a Howard Hughes Medical Institute investigator
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available