Suppression of brain cholesterol synthesis in male Mecp2-deficient mice is age dependent and not accompanied by a concurrent change in the rate of fatty acid synthesis

Adam M. Lopez, Jen Chieh Chuang, Kenneth S. Posey, Stephen D. Turley

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2) are the principal cause of Rett syndrome, a progressive neurodevelopmental disorder afflicting 1 in 10,000 to 15,000 females. Studies using hemizygous Mecp2 mouse models have revealed disruptions to some aspects of their lipid metabolism including a partial suppression of cholesterol synthesis in the brains of mature Mecp2 mutants. The present studies investigated whether this suppression is evident from early neonatal life, or becomes manifest at a later stage of development. We measured the rate of cholesterol synthesis, in vivo, in the brains of male Mecp2 /y and their Mecp2+/y littermates at 7, 14, 21, 28, 42 and 56 days of age. Brain weight was consistently lower in the Mecp2−/y mice than in their Mecp2+/y controls except at 7 days of age. In the 7- and 14-day-old mice there was no genotypic difference in the rate of brain cholesterol synthesis but, from 21 days and later, it was always marginally lower in the Mecp2−/y mice than in age-matched Mecp2+/y littermates. At no age was a genotypic difference detected in either the rate of fatty acid synthesis or cholesterol concentration in the brain. Cholesterol synthesis rates in the liver and lungs of 56-day-old Mecp2−/y mice were normal. The onset of lower rates of brain cholesterol synthesis at about the time closure of the blood brain barrier purportedly occurs might signify a disruption to mechanism(s) that dictate intracellular levels of cholesterol metabolites including oxysterols known to exert a regulatory influence on the cholesterol biosynthetic pathway.

Original languageEnglish (US)
Pages (from-to)77-84
Number of pages8
JournalBrain Research
Volume1654
DOIs
StatePublished - Jan 1 2017

Keywords

  • Brain weight
  • Desmosterol
  • Fatty acid synthesis
  • Ontogeny
  • Rett syndrome

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Developmental Biology
  • Clinical Neurology

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