title: Abnormalities in brain biochemistry associated with lack of dystrophin: studies of the mdx mouse.
abstract: Biochemical abnormalities have been reported in dystrophin-deficient muscle of boys with Duchenne (severe Xp21) muscular dystrophy or in the murine (mdx) model of the disease. These abnormalities include altered energy metabolism and responses to osmotic shock. In contrast, the situation in brain is less well understood and it is probable that dystrophin is playing a different role (or roles) in this organ. In this study we conclude that the elevation in choline-containing compounds reported in mdx brain is confined to cerebellum and hippocampus in older (> 6 months) mice. We report alterations in glucose metabolism in mdx brain under normal, awake conditions, and a reduced response of brain metabolism to the gamma-aminobutyric acid(A) receptor agonist muscimol. Using brain cortical slices we found no difference in the response of dystrophic tissue to hypoosmotic shock, but increased, substrate-dependent oxygen consumption rates at low oxygen partial pressures.
authors.affiliation: Department of Biochemistry, The University of Sydney, Sydney, NSW 2006, Australia. crae@biochem.usyd.edu.au
authors.forename: Caroline
authors.initials: C
authors.lastname: Rae
authors.forename: Julian L
authors.initials: JL
authors.lastname: Griffin
authors.forename: Duncan H
authors.initials: DH
authors.lastname: Blair
authors.forename: John H
authors.initials: JH
authors.lastname: Bothwell
authors.forename: William A
authors.initials: WA
authors.lastname: Bubb
authors.forename: Annie
authors.initials: A
authors.lastname: Maitland
authors.forename: Stewart
authors.initials: S
authors.lastname: Head
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D016189:Dystrophin / Q000172:deficiency* / Q000235:genetics; D005260:Female; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009118:Muscimol / Q000494:pharmacology; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism; D010101:Oxygen Consumption; D011963:Receptors, GABA-A / Q000378:metabolism; D012016:Reference Values
chemical_list: D016189:Dystrophin; D011963:Receptors, GABA-A; D009118:Muscimol; D005947:Glucose; D002794:Choline