Project Detail
Interagency Autism Coordinating Committee (IACC) logo
Office of Autism Research Coordination (OARC) logo

MeCP2 modulation of BDNF signaling: Shared mechanisms of Rett and autism  

Rett syndrome (RTT), an autism spectrum disorder, is caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2), a transcriptional regulator that binds to methylated CpG sites in promoter regions of DNA. An imbalance of excitatory and inhibitory synaptic function in the hippocampus has been implicated in neurodevelopmental disorders associated with cognitive impairments and mental retardation. Mouse cortical neurons lacking Mecp2 show low levels of neuronal activity caused by an excitation/inhibition imbalance that favors synaptic inhibition, and Mecp2 expression levels modulate excitatory synapse formation between hippocampal neurons. One of the target genes of Mecp2 transcriptional control is Brain-derived neurotrophic factor (Bdnf), a potent modulator of activity-dependent synaptic development, function and plasticity. This research will use mouse models to test whether impaired development of hippocampal inhibitory synapses due to reduced BDNF release contributes to the excitatory/inhibitory imbalance of synaptic function implicated in cognitive impairments and autism in RTT. These experiments will uncover fundamental brain mechanisms involved in the neuropathology of RTT and autism spectrum disorders and test an experimental rationale to relieve cognitive impairments and mental retardation in children with associated neurodevelopmental disorders. Project Status


Funder National Institutes of Health
Fiscal Year Funding $320,469.00
Current Award Period 2010-2015
Project Number 1R01NS065027-01A1
Principal Investigator Pozzo-Miller, Lucas
Received ARRA Funding? No
Strategic Plan Question Question 2: How Can I Understand What Is Happening? (Biology)
Subcategory Molecular Pathways
Strategic Plan Objective Green dot: Objective has greater than or equal to the recommended funding. 2SD. Launch three studies that target improved understanding of the underlying biological pathways of genetic conditions related to autism (e.g. Fragile X, Rett syndrome, tuberous sclerosis complex) and how these conditions inform risk assessment and individualized intervention by 2012. IACC Recommended Budget: $9,000,000 over 5 years.
Federal or Private? Federal
Institution University of Alabama at Birmingham
State/Country Alabama
Web Link 1 MeCP2 modulation of BDNF signaling: Shared mechanisms of Rett and autism (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
History/Related Projects N/A