Impact of Choline intake during pregnancy on maternal cognition and hippocampal gene signature in old age
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 old age in mouse model. 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 old age, 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 old age. 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 supplement benefits women's cognitive health during pregnancy and at the old age. Overall design: RNA profiling was performed on hippocampal tissue from 15-month-old mice, including non-pregnant (nulliparous) and pregnant (multiparous) mice on a normal diet as controls, as well as pregnant mice on either a choline-supplemented or intermittent choline deprivation diet given during pregnancy. The goal was to assess the effects of pregnancy and choline diet during pregnancy on hippocampal gene expression in old age. Eight-week-old young mice were also included in the analysis.