Prenatal maternal factors in the development of cognitive impairments in the offspring

Different environmental factors acting during sensitive prenatal periods can have a negative impact on neurodevelopment and predispose the individual to the development of various psychiatric conditions that often share cognitive impairments as a common component. As cognitive symptoms remain one of the most challenging and resistant aspects of mental illness to be treated pharmacologically, it is important to investigate the mechanisms underlying such cognitive deficits, with particular focus on the impact of early life adverse events that predispose the individual to mental disorders. Multiple clinical studies have, in fact, repeatedly confirmed that prenatal maternal factors, such as infection, stress or malnutrition, are pivotal in shaping behavioral and cognitive functions of the offspring, and in the past decade many preclinical studies have investigated this hypothesis. The purpose of this review is to describe recent preclinical studies aimed at dissecting the relative impact of various prenatal maternal factors on the development of cognitive impairments in offspring, focusing on animal models of prenatal stress and prenatal infection. These recent studies point to the pivotal role of prenatal stressful experiences in shaping memory and learning functions associated with specific brain structures, such as the hippocampus and the prefrontal cortex. More importantly, such experimental evidence suggests that different insults converge on similar downstream functional targets, such as cognition, which may therefore represent an endophenotype for several pathological conditions. Future studies should thus focus on investigating the mechanisms contributing to the convergent action of different prenatal insults in order to identify targets for novel therapeutic intervention.