Prenatal stress alters glutamatergic system responsiveness in adult rat prefrontal cortex.

Exposure to stress during gestation alters brain development resulting in permanent alterations that may increase susceptibility to subsequent cognitive or neuropsychiatric disorders. In this manuscript we examined the effects of prenatal stress on critical determinants of the glutamatergic synapse under basal conditions as well as in response to acute stress. The main finding of this work is that gestational stress altered the responsiveness of the glutamatergic system following a challenge at adulthood. In fact, while in control animals acute swim stress enhanced the phosphorylation levels of the NMDA receptor subunits NR-1(Ser896) and NR-2B(Ser1303) as well as the phosphorylation levels of alpha calcium/calmodulin-dependent protein kinase II (Thr286), a crucial sensor of calcium fluctuations, prenatal stress prevented or attenuated such activation. This dynamic modulation is restricted to prefrontal cortex since no changes were observed in the hippocampus, in line with the different maturational profile of these brain regions. Changes were also observed in the phosphorylation of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate subunit GluR-1(Ser831) which, however, relied on the acute stress exposure and were independent of gestational stress. These effects point to a unique interference of chronic prenatal stress with the responsiveness of specific determinants of the glutamatergic synapse at adulthood in a region specific manner. The inability to mount an homeostatic glutamatergic response to subsequent stress at adulthood may impair the normal responses of the cell to challenging situations.