Quantitative changes in hippocampal microvasculature of chronically stressed rats: No effect of fluoxetine treatment

Abstract

Exposure to chronic stress alters the number and morphology of neurons and glia in the hippocampal formation; however, little is known about possible changes in vasculature. Here, we examined the effect of chronic social defeat stress on hippocampal vascular supply in rats. Recent reports document that antidepressant treatment can influence angiogenesis in the hippocampus; therefore, we also studied the effect of antidepressant drug treatment on hippocampal capillarization. Animals were subjected to 5 weeks of daily social defeat by an aggressive conspecific and received concomitant, daily, oral fluoxetine (10 mg/kg) treatment during the last 4 weeks. Rat endothelial cell antigen-1 (RECA-1)-labeling of capillaries and quantitative stereological techniques were used to evaluate the treatment effects on capillary number. Special attention was paid to analysis of the vascular supply of the subgranular zone, which is regarded as an important component of the neurogenic niche for adult hippocampal neurogenesis. Chronic stress significantly decreased the number of microvessels by 30% in all hippocampal subregions, whereas fluoxetine treatment had no influence on capillary number. Furthermore, chronic stress decreased the capillarization of the subgranular zone to a similar extent, indicating that chronic stress affects the vascular niche for adult hippocampal neurogenesis. However, fluoxetine treatment had no impact on capillarization in the subgranular zone. We also detected a decrease in hippocampal volume in the animals as a result of stress, which was mildly altered by fluoxetine treatment. These pronounced changes in vascular supply may explain why the hippocampus is more vulnerable to insults when chronic stress precedes or coincides with other harmful conditions. Reduced microvasculature may also contribute to hippocampal volume decrease in stress-related disorders.