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Neurochemical changes in a mouse model of Rett syndrome: changes over time and in response to perinatal choline nutritional supplementation
Author(s) -
Ward Bonnie C.,
Kolodny Nancy H.,
Nag Nupur,
BergerSweeney Joanne E.
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05768.x
Subject(s) - rett syndrome , mecp2 , choline , glutamine , endocrinology , neurochemical , medicine , glutamate receptor , wild type , mutant , biology , neuroscience , biochemistry , amino acid , gene , receptor , phenotype
Rett syndrome (RTT), the second leading cause of mental retardation in girls, is caused by mutations in the X‐linked gene for methyl‐CpG‐binding protein 2 (MeCP2), a transcriptional repressor. In addition to well‐documented neuroanatomical and behavioral deficits, RTT is characterized by reduced markers of cholinergic activity and general neuronal health. Previously, we have shown that early postnatal choline (Cho) supplementation improves behavioral and neuroanatomical symptoms in a mouse model of RTT ( Mecp2 1lox mice). In this study, we use NMR spectroscopy to quantify the relative amounts of Cho, Glutamate (Glu), Glutamine (Gln), and N ‐acetyl aspartate (NAA) in the brains of wild type and mutant mice at 21, 35, and 42 days of age and in mice receiving postnatal Cho supplementation. We find that the mutant mice have reduced levels of Cho, Glu, and NAA, but elevated Gln levels, compared with their wild type littermates. These differences emerge at different developmental ages. Cho supplementation increases NAA levels, a marker of neuronal integrity, but has no effect on Cho, Glu, or Gln. These data suggest that postnatal nutritional supplementation may improve neuronal function and could serve as a therapeutic agent for human RTT patients.