Cellular and molecular signatures of motherhood in the adult and ageing rat brain.

Pregnancy is marked by robust changes, including brain changes to volume, structure, connectivity and neuroplasticity. Although some brain changes are restricted to pregnancy and the postpartum, others are long-lasting. Few studies have examined possible mechanisms of these changes or the effects of multiple pregnancies. We characterized various cellular and molecular signatures of parity (nulliparous, primiparous, biparous) in the rat hippocampus. We investigated density of neural stems cells (Sox2), microglia (Iba-1) and levels of a synaptic protein (PSD-95), cell signalling pathways, neuroinflammation, and the tryptophan-kynurenine (TRP-KYN) pathway, one week after weaning their pups from the last pregnancy (age of dam: seven months) and in middle-age (age of dam: 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 (pp70S6K, S6RP) and number of microglia in the dentate gyrus, regardless of age. Parity resulted in transient changes to the TRP-KYN system. Thus, previous parity has lasting effects on synaptic plasticity with fewer lasting effects on inflammation and cell signalling phosphoproteins in the whole hippocampus.