| High levels of stress and, by association, glucocorticoids, are reported to increase neuronal susceptibility to various insults, including ischemia. The purpose of the current study was to examine the possibility that chronic mild stress (CMS) exacerbates the neural consequences of permanent bilateral occlusion of the common carotid arteries (2VO) in the adult rat. To this end, 8-month old male rats were assigned to 2VO and control conditions. At approximately 7 days post-surgery, control and 2VO animals were assigned to stress and non-stress conditions. Animals in the stress condition were exposed to a six-week chronic mild stress regime. At eight weeks post-surgery, 2VO rats exhibited significantly more CAI pyramidal cell loss compared to sham animals, with Stress 2VO rats exhibiting the largest loss of CAI pyramidal cells. Stress, by itself, did not result in significant CAI cell loss. In contrast, stress promoted a significant reduction in glial fibrillary acidic protein (GFAP) expression in Stress 2VO and Stress Sham animals. No differences in brain-derived neurotrophic factor (BDNF) expression, the number of degenerating cells as quantified by Fluoro-Jade staining, or corticosterone levels were observed between groups. The results of this study suggest that chronic mild stress leaves hippocampal cells vulnerable to ischemic insult by altering their metabolic state. Since cerebral hypoperfusion is characteristic of mild cognitive impairment, probably the progenitor stage of Alzheimer's disease (AD), and since CA1 cell loss is an established feature of AD, exposure to CMS and higher levels of circulating glucocorticoids may potentiate the progression of neuropathology in AD. |
