Cognitive impairment induced by permanent bilateral common carotid occlusion exacerbates depression-related behavioral, biochemical, immunological and neuronal markers

摘要

There is a strong link between cognitive impairment and depression, but up to date it is not clear whether cognitive impairment is 'cause' or 'consequence' of depression. Therefore, we here examined the effect of cognitive impairment induced by permanent occlusion of common carotid arteries, a model known as two-vessel occlusion (2VO), on chronic unpredictable stress (CUS)-induced depression-related markers in rats. Male Sprague-Dawley rats underwent 2VO or sham surgery. Sixty days after the surgery, the cognitive function of the rats was tested using the radial arm maze task measuring working and reference memory. Subsequently, the animals were randomly assigned to undergo 21 days of CUS or to stay non-stressed. One week after the last stressor, psychomotor retardation, a feature of depression-like behavior, was assessed using the forced swim test (FST) by measuring time spent on immobility. Plasma amino acid (glutamine, glutamate and glycine) and serum pro-inflammatory cytokine (interleukin 6) levels, and hippocampus CA1 neuronal damage were measured 24 h after FST exposure. Results show that 2VO increased immobility in the FST only when rats had been exposed to CUS. In addition, 2VO surgery intensified the effect of CUS on IL-6, glutamate and glycine levels and increased