Chronic psychosocial stress impairs early LTP but not late LTP in the dentate gyrus of at-risk rat model of Alzheimer's disease.

The CA1 and dentate gyrus regions of the hippocampus are physically and functionally closely related but they react differently to insults. This study examined the effect of chronic psychosocial stress on the dentate gyrus of an at-risk (preclinical) rat model of Alzheimer's disease (subAβ rats). Chronic psychosocial stress was produced using a rat intruder model. The at-risk rat model of Alzheimer's disease was created by osmotic pump infusion of sub-pathological dose of Aβ (160 pmol Aβ1-42/day i.c.v) for 14 days. Electrophysiological methods were used to evoke and record early and late phase LTP in the dentate gyrus of anesthetized rats, and immunoblotting was used to measure levels of memory-related signaling molecules in the same region. Electrophysiological and molecular tests in the dentate gyrus showed that subAβ rats or stressed rats were not different from control rats. However, when the subAβ rats were chronically stressed, the combined treatments severely suppressed early phase LTP without affecting the late phase LTP of dentate gyrus. Additionally, in the chronically stressed subAβ rats the expected elevation of levels of phosphorylated CaMKII did not materialize after expression of early phase LTP suggesting impaired phosphorylation, which may explain the severely blocked early phase LTP.