Choline intake during pregnancy influences maternal cognitive function and hippocampal gene expression in late adulthood

Background and objective: Women are twice as likely to have Alzheimer's disease (AD) than men and multiparity has been suggested to be a risk factor for dementia. The present study evaluated whether the lack of certain nutrients during pregnancy influences cognition while pregnant and in late adulthood using mouse model. Methods: Non-targeted NMR analysis was conducted to assess changes in plasma nutrients and metabolites on gestation day 7.5 compared to day 1. Effects of choline intake during pregnancy on cognition and general health were evaluated in consecutive pregnancies. Mice were assigned to groups with normal diet, cholinesupplemented diet, or choline-deficient diet during pregnancy. Non-pregnant mice were included as controls. Behavioral analyses were performed during the second half of the first and fourth pregnancies, as well as at 12 and 15 months of age. The hippocampus was collected for RNA-seq analysis at 15 months of age. Results and conclusion: Non-targeted NMR analysis revealed significantly lower levels of numerous plasma nutrients and metabolites including choline and its derivatives on gestation day 7 compared to day 1. Novel object recognition and Morris Water Maze tests revealed impaired cognition in pregnant mice compared to nonpregnant controls. Choline deprivation worsened the cognitive impairment during pregnancy and choline supplementation alleviated it. Furthermore, choline availability during pregnancy affected cognition and general health in late adulthood, with mice given a choline-deficient diet during pregnancy performed more poorly. RNA-Seq analysis indicates lasting effect of choline intake during pregnancy on hippocampal gene signatures in late adulthood. Choline deprivation was associated with more upregulation of proinflammatory genes, whereas choline supplementation showed upregulation of neuroprotective genes such as Prl, Gh, and hemoglobin (Hba and Hbb subunits). Together, the study shows that choline supplementation benefits cognitive health in women during pregnancy and in late adulthood.