Hippocampal Protein Kinase C Gamma Signaling Mediates the Impairment of Spatial Learning and Memory in Prenatally Stressed Offspring Rats.

Substantial evidence has demonstrated that prenatal stress (PS) impairs spatial learning and memory in offspring. The neuron-specific protein kinase C gamma (PKCγ) has been proposed to be unique in spatial learning and memory. The present study proposes to determine whether hippocampal PKCγ is involved in the detrimental effects of PS on spatial learning and memory in offspring, and to further explore the effects of PS-induced PKCγ-dependent growth-associated protein 43 (GAP-43) and neurogranin (Ng) phosphorylation alteration on calcium/calmodulin-dependent protein kinase II (CaMKII) activation. Prenatal restraint stress models were established, and lentivirus-mediated overexpression of PKCγ in the hippocampal CA1 area was applied. The results demonstrated that PS impaired spatial learning acquisition and memory retrieval on the Morris Water Maze test, especially in juvenile female rats. Hippocampal PKCγ membrane translocation and cytosolic PKCγ levels were decreased in PS females. The expression of phosphorylated GAP-43 (p-GAP-43) and phosphorylated Ng (p-Ng), as well as phosphorylated CaMKII (p-CaMKII), was significantly reduced in the hippocampus of PS females. Overexpression of PKCγ in the hippocampal CA1 area recovered the ability of spatial learning and memory in PS female offspring. Furthermore, enhancing PKCγ reversed PS-induced membrane and cytosolic PKCγ reduction, and restored levels of GAP-43 and Ng phosphorylation, and CaMKII activation in the hippocampus. In conclusion, PS possibly decreases hippocampal PKCγ activity, resulting in a reduction of p-GAP-43 and p-Ng, which underlies insufficient CaMKII activation, thereby impairing spatial learning and memory.