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

摘要

Substantial evidence has demonstrated that prenatal stress (PS) impairs spatial learning and memory in offspring. The neuron-specific protein kinase C gamma (PKC gamma) has been proposed to be unique in spatial learning and memory. The present study proposes to determine whether hippocampal PKC gamma is involved in the detrimental effects of PS on spatial learning and memory in offspring, and to further explore the effects of PS-induced PKC gamma-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 PKC gamma in the hippocampal CA1 area was applied. The results demonstrated that PS impaired spatial learning acquisition and memory retrieval on the MorrisWater Maze test, especially in juvenile female rats. Hippocampal PKC gamma membrane translocation and cytosolic PKC gamma 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 PKC gamma in the hippocampal CA1 area recovered the ability of spatial learning and memory in PS female offspring. Furthermore, enhancing PKC gamma reversed PS-induced membrane and cytosolic PKC gamma reduction, and restored levels of GAP-43 and Ng phosphorylation, and CaMKII activation in the hippocampus. In conclusion, PS possibly decreases hippocampal PKC gamma activity, resulting in a reduction of p-GAP-43 and p-Ng, which underlies insufficient CaMKII activation, thereby impairing spatial learning and memory. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.