Impaired social cognition caused by perinatal protein malnutrition evokes psychiatric-like disorders and is intergenerationally transmitted.

Maternal malnutrition remains one the major early-life adversities contributing poor health in one in five children worldwide. Clinical studies demonstrate that malnourished children are growth-impaired, exhibit behavioral changes and suffer from cognitive impairments. These health effects can persist even if nutrition becomes adequate later in life. Experimental studies on rodents have shown that maternal protein restriction is associated with the emergence of several adverse effects of offspring neurological development. In addition, reported effects of prenatal and/or postnatal protein malnutrition on the offspring include changes in exploratory behavior and anxiety, altered learning and memory abilities and a different response to aversive stimuli. These behavioral alterations characterize the symptoms of various psychiatric disorders that has been increasingly regarded as developmental disorders. Social behavioral deficits in psychiatric diseases have been hypothesized to arise form elevation in the cellular balance of excitation and inhibition within the cortex generally, and PFC specifically. Such imbalance may be caused either by increased activity in excitatory neurons or by reduction in inhibitory neuron function. Interestingly, decreases in inhibitory neurotransmission are a common finding in animal models of ASD. In addition, direct alterations of E/I balance within the PFC in adult mice have strong effect on social motivation. The critical question we have posed in this work is whether maternal protein malnutrition alters the offspring’s social cognition and if this were the case, if these behavioral deficits are transmitted to the following generation. We hypothesized that at the basis of such alterations in social cognition underlie changes in gene expression related to E/I signaling within the mPFC. Our results focus on damaging effects of maternal protein malnutrition even for generations that are not exposed to this environmental adversity.