Maternal protein restriction around conception increases foetal neuronal differentiation and is associated with adult memory deficits

Willaime-Morawek, Sandrine (2017) Maternal protein restriction around conception increases foetal neuronal differentiation and is associated with adult memory deficits. In BNA2017 Abstract book. British Neuroscience Association..

Record type: Conference or Workshop Item (Paper)

Abstract

Maternal malnutrition during pregnancy is detrimental to foetal development and increases the risk of many chronic diseases in later life i.e. increased risk of schizophrenia. Previous studies have shown maternal protein malnutrition during pregnancy and lactation compromises brain development in late gestation and after birth, affecting structural, biochemical and pathway dynamics with lasting consequences for motor and cognitive function. However, the importance of nutrition during embryogenesis for early brain development is unknown. We have previously shown maternal low protein diet confined to the preimplantation period (Emb-LPD) in mice is sufficient to induce cardiometabolic and behavioural abnormalities in adult offspring. Using the same diet model, female mice were fed different diets from conception to the end of pregnancy: normal protein diet (NPD), low protein diet (LPD) or embryonic LPD (Emb-LPD: LPD for 3.5 days, NPD thereafter). Foetal brains were analysed during gestation with in vivo analysis using FACS and immunofluorescence for neurogenesis markers, and in vitro techniques using the neurosphere assay. Follow up behavioural tests in the offspring were performed, including the short-term memory novel object recognition. We have shown that Emb-LPD and sustained LPD reduce neural stem and progenitor cell numbers through decreased proliferation in both ganglionic eminences and cortex of the foetal brain at E12.5, E14.5 & E17.5 (p=0.001). Moreover, Emb-LPD causes remaining neural stem cells to upregulate the neuronal differentiation rate in compensation beyond control levels during gestation, independently of sex (p<0.001). When analysing the adult offspring behaviour, the Emb-LPD males and females show a clear deficit in short-term memory (p=0.00001). Our data are the first to demonstrateclearly that poor maternal nutrition around conception has adverse effects on early brain development and is associated with adult memory deficits.

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