Temporal and regional alterations in NMDA receptor expression in Mecp2-null mice.

Mark McIntosh,'s picture
PubMed URL: 
http://www.ncbi.nlm.nih.gov/pubmed/21901842
Author: 
Johnston MV
Author List: 
Blue ME
Kaufmann WE
Bressler J
Eyring C
O'driscoll C
Naidu S
Johnston MV
Journal: 
Anat Rec (Hoboken)
PubMed ID: 
21901842
Pagination: 
1624-34
Volume: 
294
Issue: 
10
Abstract: 
Our previous postmortem study of girls with Rett Syndrome (RTT), a development disorder caused by MECP2 mutations, found increases in the density of N-Methyl-D-aspartate (NMDA) receptors in the prefrontal cortex of 2-8-year-old girls, whereas girls older than 10 years had reductions in NMDA receptors compared with age-matched controls (Blue et al., Ann Neurol 1999b;45:541-545). Using [(3)H]-CGP to label NMDA-type glutamate receptors in 2- and 7-week old wild-type (WT), Mecp2-null, and Mecp2-heterozygous (HET) mice (Bird model), we found that frontal areas of the brain also exhibited a bimodal pattern in NMDA expression, with increased densities of NMDA receptors in Mecp2-null mice at 2 weeks of age but decreased densities at 7 weeks of age. Visual cortex showed a similar pattern, while other cortical regions only exhibited changes in NMDA receptor densities at 2 weeks (retrosplenial granular) or 7 weeks (somatosensory). In thalamus of null mice, NMDA receptors were increased at 2 and 7 weeks. No significant differences in density were found between HET and WT mice at both ages. Western blots for NMDAR1 expression in frontal brain showed higher levels of expression in Mecp2-null mice at 2 weeks of age but not at 1 or 7 weeks of age. Our mouse data support the notion that deficient MeCP2 function is the primary cause of the NMDA receptor changes we observed in RTT. Furthermore, the findings of regional and temporal differences in NMDA expression illustrate the importance of age and brain region in evaluating different genotypes of mice.
Published Date: 
October, 2011

Appointments & Referrals

FIND A SPECIALIST

Publications

Read inspiring stories, news and updates about the Institute's patient care, research, special education, professional training, and community programs.

 

Resource Finder

 

A free resource that provides access to information and support for individuals and families living with developmental disabilities.