Cholinergic hypofunction in MeCP2-308 mice: beneficial neurobehavioural effects of neonatal choline supplementation

Behav Brain Res. 2011 Aug 10;221(2):623-9. doi: 10.1016/j.bbr.2011.03.051. Epub 2011 Mar 30.

Abstract

We studied the long-term effects of a postnatal choline supplementation (from birth till weaning) in the truncated MeCP2-308 mouse model of Rett syndrome. Adult male mutant hemizygous (hz) mice showed a reduction of locomotor activity compared to wild type (wt) littermates. Early choline treatment restored wt-like locomotor activity levels in hz mice. Reduced striatal choline acetyl transferase (ChAT) activity and decreased levels of cortical mRNA NGF were found in hz mice. Choline supplementation increased striatal ChAT activity and also enhanced NGF and BDNF expression in cortical and hippocampal regions. As a whole, postnatal choline supplementation attenuates some of the behavioural and neurobiological abnormalities of the Mecp2-308 phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Choline / administration & dosage
  • Choline / pharmacology
  • Choline / therapeutic use*
  • Choline O-Acetyltransferase / metabolism
  • Cholinergic Fibers / drug effects*
  • Cholinergic Fibers / physiology
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Dietary Supplements*
  • Disease Models, Animal
  • Exploratory Behavior / drug effects
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Methyl-CpG-Binding Protein 2 / genetics
  • Mice
  • Mice, Mutant Strains
  • Motor Activity / drug effects
  • Nerve Growth Factor / metabolism
  • Rett Syndrome / diet therapy*
  • Rett Syndrome / metabolism
  • Rett Syndrome / physiopathology
  • Rett Syndrome / psychology*
  • Scopolamine / pharmacology

Substances

  • Brain-Derived Neurotrophic Factor
  • Methyl-CpG-Binding Protein 2
  • Nerve Growth Factor
  • Scopolamine
  • Choline O-Acetyltransferase
  • Choline