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

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.

► Neonatal choline supplementation normalized locomotor activity levels in Mecp2-308 mice.
► Neonatal choline supplementation increased striatal choline acetyl transferase enzymatic activity.
► Neonatal choline increased BDNF and NGF levels in Mecp2-308 and wt mice.
► Signs of hypofunction of central cholinergic populations in Mecp2-308 mice.