Abstract
Rett syndrome is a developmental disorder that restricts brain growth beginning in
the first year of life and evidence from neuropathology and neuroimaging indicates
that axonodendritic connections are especially vulnerable. In a study of amino acid
neurotransmitter receptors using receptor autoradiography in tissue slices of frontal
cortex and the basal ganglia, we found a biphasic age-related pattern with relatively
high receptor densities in young RS girls and lower densities at later time. Using
microarray analysis of gene expression in frontal cortex, we found that some of the
most prominent alterations occurred in gene products related to synapses, including
the NMDA receptor NR1 subunit, the cytoskeletal protein MAP-2 and synaptic vesicle
proteins. Using a new antibody that recognizes MeCP2, the transcription factor mutated
in RS, we established that most neurons in the rodent brain express this transcription
factor. We hypothesize that a major effect of mutations in the MeCP2 protein is to
cause age-related disruption of synaptic proliferation and pruning in the first decade
of life.
Keywords
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Article info
Footnotes
☆Presented at the World Congress on Rett Syndrome 2000, Karuizawa, Japan, July, 2000.
Identification
Copyright
© 2001 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
