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.

Epigenetic effects of folate and related B vitamins on brain health throughout life: Scientific substantiation and translation of the evidence for health improvement strategies.

Suboptimal status of folate and/or interrelated B vitamins (B12 , B6 and riboflavin) can perturb one-carbon metabolism and adversely affect brain development in early life and brain function in later life. Human studies show that maternal folate status during pregnancy is associated with cognitive development in the child, whilst optimal B vitamin status may help to prevent cognitive dysfunction in later life. The biological mechanisms explaining these relationships are not clear but may involve folate-related DNA methylation of epigenetically controlled genes related to brain development and function. A better understanding of the mechanisms linking these B vitamins and the epigenome with brain health at critical stages of the lifecycle is necessary to support evidence-based health improvement strategies. The EpiBrain project, a transnational collaboration involving partners in the United Kingdom, Canada and Spain, is investigating the nutrition-epigenome-brain relationship, particularly focussing on folate-related epigenetic effects in relation to brain health outcomes. We are conducting new epigenetics analysis on bio-banked samples from existing well-characterised cohorts and randomised trials conducted in pregnancy and later life. Dietary, nutrient biomarker and epigenetic data will be linked with brain outcomes in children and older adults. In addition, we will investigate the nutrition-epigenome-brain relationship in B vitamin intervention trial participants using magnetoencephalography, a state-of-the-art neuroimaging modality to assess neuronal functioning. The project outcomes will provide an improved understanding of the role of folate and related B vitamins in brain health, and the epigenetic mechanisms involved. The results are expected to provide scientific substantiation to support nutritional strategies for better brain health across the lifecycle.