Permanent improvement in deficient sensory inhibition in DBA/2 mice with increased perinatal choline

Abstract

Rationale: Schizophrenia patients and certain inbred mouse strains (i.e., DBA/2) show deficient sensory inhibition which has been linked to reduced numbers of hippocampal alpha7 nicotinic receptors and to underlying polymorphisms in the promoter region for the alpha7 gene. Increasing maternal dietary choline, a selective alpha7 agonist, during gestation has been shown to produce long-term changes in adult offspring behavior (i.e., improved learning and memory in rats).

Objectives: The objective of this study is to improve sensory inhibition in DBA/2 mice through maternal choline supplementation.

Materials and methods: DBA/2 dams were placed on normal (1.1 g/kg) or supplemented (5 g/kg) choline diet throughout gestation and lactation. Offspring were placed on normal diet at weaning and were assessed for sensory inhibition parameters at adulthood. Evoked EEG responses to identical paired auditory stimuli were compared. At the end of the study, the brains were collected for autoradiographic assessment of hippocampal levels of alpha-bungarotoxin binding to visualize alpha7 nicotinic receptors.

Results: Offspring mice which were choline supplemented during gestation showed significantly improved sensory inhibition compared to mice gestated on the normal choline diet. The improvement was produced by a significant reduction in the response to the second stimulus, demonstrating improved inhibition to that stimulus. There was a concurrent increase in alpha7 receptor numbers in both the CA1 and dentate gyrus regions of the hippocampus suggesting that this increase may be responsible for the improved inhibition.

Conclusions: These data show that gestational choline supplementation produces permanent improvement in a deficit associated with schizophrenia and may have implications for human prenatal nutrition.