Modulation of noradrenergic signalling reverses stress-induced changes in the hippocampus: Involvement of orexinergic systems

Abstract

Stress can be beneficial for adapting to dangerous situations in the short term but can be damaging in the long term, especially in the hippocampus. The noradrenergic and orexinergic systems play important roles in stress response. This study investigated the effect of noradrenergic activation on changes induced by chronic stress in the hippocampus and the involvement of orexinergic modulation in this process.

This study examined five groups of 40 male Wistar rats (4 + 4 animals/ group): control, chronic stress, acute stress, control with noradrenergic activation, and chronic stress with noradrenergic activation. Hippocampal tissue and blood plasma were the primary specimens analyzed. The researchers measured plasma corticosterone (CORT) using a fluorometric method, examined the expression of prepro-orexin (prepro-OX), orexin receptor-1 (OXr1), and glucocorticoid receptor (GR) through RT-PCR, and quantified neuronal populations using Nissl staining.

Acute and chronic stress increased plasma CORT levels and gene expression of prepro-OX, OXr1, and GR, while decreasing neuronal numbers, with chronic stress having a more pronounced effect. Yohimbine-treated and/or stressed rats exhibited elevated plasma CORT levels. Chronic stress substantially upregulated GR and increased prepro-OX and OXr1 expressions whereas yohimbine recovered those profiles in chronically stressed animals. Conversely, chronic stress reduced hippocampal neuronal populations, and chronic stress combined with yohimbine partially compensated for the neuronal numbers compared to chronic stress alone.

These results suggest that noradrenergic signalling can reverse chronic stress-induced impairments in prepro-OX, OXr1 and GR expressions, and neuronal populations.