Long-term cellular and molecular signatures of pregnancy in the adult and ageing brain

Abstract

Pregnancy is marked by brain changes to volume, structure, connectivity, some of which are long-lasting. Few studies have examined possible mechanisms of these changes or the effects of multiple pregnancies. Here, we characterized various cellular and molecular signatures of parity (nulliparous, primiparous, biparous) in the hippocampus, an important area for cognitive and emotional regulation, and in plasma. We investigated density of neural stems cells (Sox2) and microglia (Iba-1), and levels of the postsynaptic density protein (PSD-95), cell signalling pathways, hippocampal and peripheral inflammation and the tryptophan-kynurenine (TRP-KYN) pathway, at 1 week after weaning (7 months) and in middle-age (13 months). Parity increased PSD-95 levels in both age groups and prevented the age-related decrease in neural stem cell density observed in nulliparous rats. Biparity increased cell signalling phosphoproteins (pp706sk, S6RP) and number of microglia in the dentate gyrus, regardless of age. Parity resulted in transient changes to the TRP-KYN system and peripheral inflammation. Thus, parity has lasting effects on synaptic plasticity and alters the trajectory of hippocampal aging. Highlights- Parity increased the postsynaptic protein PSD-95 in the hippocampus, regardless of age. - Biparity increased microglial density and cell signalling in the hippocampus, regardless of age. - Parity prevented the age-related decline in hippocampal neural stem cells. - Parity transiently increased tryptophan-kynurenine pathway metabolites. - Aging reduced plasma cytokine levels, an effect more prominent with nulliparity.