Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory

Significance Maternal protein malnutrition during pregnancy and lactation compromises brain development, with lasting consequences for motor and cognitive function. However, the importance of nutrition on early brain development is unknown. We have previously shown that maternal low-protein diet confined to the preimplantation period (Emb-LPD) in mice, with normal nutrition thereafter, is sufficient to induce cardiometabolic and locomotor behavioral abnormalities in adult offspring. Here, we report that Emb-LPD and sustained LPD reduce neural stem cells (NSCs) in the fetal brain. Moreover, Emb-LPD causes remaining NSCs to upregulate neuronal differentiation in compensation beyond control levels and increase cortex thickness and neuron ratio, leading to adult memory deficits. These data demonstrate that poor maternal nutrition from conception adversely affects brain development and adult memory.