Chronic psychosocial stress decreases calcineurin in the dentate gyrus: a possible mechanism for preservation of early ltp

Abstract

Chronic psychosocial stress impairs early long-term potentiation (LTP) in the hippocampal CA1 region but not in the dentate gyrus of anesthetized rats. Analysis of putative signaling molecules involved in the expression of LTP was performed to determine the possible reason(s) for the apparent resistance of the LTP of the dentate gyrus to chronic psychosocial stress. Immunoblotting was used to determine possible changes in the basal levels of various fractions of calcium-dependent calmodulin kinase II (CaMKII), phosphorylated CaMKII (P-CaMKII), calmodulin, protein kinase C gamma (PKCγ) and calcineurin in the dentate gyrus of chronically stressed rats. Western blot analysis revealed that chronic stress significantly decreased the levels of the total CaMKII without affecting P-CaMKII levels. No significant change was detected in the levels of the upstream effectors, calmodulin and PKCγ. However, chronic stress produced a significant decrease in calcineurin levels. The data suggest that the dentate gyrus of chronically stressed rats may have developed a compensatory mechanism whereby calcineurin levels are reduced to maintain normal P-CaMKII levels, which may be responsible for the normal early LTP of the dentate gyrus of chronically stressed rats. The results of this work will increase understanding of why certain brain regions are more resistant to deleterious effects of conditions that deteriorate learning and memory.