title: Neurochemical changes in a mouse model of Rett syndrome: changes over time and in response to perinatal choline nutritional supplementation.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Wellesley College, Wellesley, MA 02481, USA.
authors.forename: Bonnie C
authors.initials: BC
authors.lastname: Ward
authors.forename: Nancy H
authors.initials: NH
authors.lastname: Kolodny
authors.forename: Nupur
authors.initials: N
authors.lastname: Nag
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Berger-Sweeney
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D002794:Choline / Q000008:administration & dosage* / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D019587:Dietary Supplements; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018697:Nootropic Agents / Q000008:administration & dosage*; D015518:Rett Syndrome / Q000178:diet therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013057:Spectrum Analysis
chemical_list: D004268:DNA-Binding Proteins; C489690:MeCP1 histone deacetylase complex, mouse; D018697:Nootropic Agents; D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; D006655:Histone Deacetylases; D003401:Creatine; D002794:Choline