Survival and differentiation of endogenous neural stem cells in the hippocampus of post-stroke depression rats

Abstract

Objective To investigate the proliferation and survival of endogenous new born cells in the hippocampus of post-stroke depression (PSD) rats. Methods Male SD rats were divided into 4 groups (n = 18): control, stroke, depression and PSD group. The animals were subjected to left middle cerebral artery occlusion (MCAO) reaulting in consistent focal cerebral infarcts, followed by an 18-day exposure to chronic mild stress (CMS) and single housing to induce PSD animal model The dynamic expression of brodmodeoxyuridine (BrdU), neuron-specific nuclear protein (NeuN) and glial fibrillary acidic protein (GFAP) in the left dentate gyrus of hippocampus were determined by immunohistochemistry or double-lable immunofluorescence staining. BrdU was a marker of new born cell, NeuN and GFAP marked that new born cell differentiated into neuron and astrocyto respectively. Results Compared with ischemia animals (232.2±8.6,123.7±2.6,136.2±2.6), in the left dentate gyrus, PSD samples had significantly less BrdU-positive cells ( 156.2±2.5, t =28.83, P < 0.01 ) on the 21st day after ischemia, and on day 30 and 45 ( 70.2±2.0, 81.2±1.1, t = 52.27, 62.08, both P < 0.01 ). The ratio of BrdU-positive cells to NeuN had decreased on day 30 (79.3%±2.8% vs 69.0%±3.4%, t =5.871, P < 0.01 )and day 45 (87.7% ±4.6% vs 78.3%±2.4%, t =4.403, P < 0.01) in PSD animals. There was a statistically significant increased proportion of BrdU-positive cells co-stained with GFAP in PSD animals compared with the ischemia ones on day 30 and45 (t =4.226, 8.945, both P < 0.01). Conclusion CMS following ischemia exerts an inhibitory effect on hippocampal survival of new born cells as well as their differentiation into neurons, while promotes new born cells differentiating into astrocytes. Key words: Cerebrovascular accident; Depressive disorder; Hippocampus; Cell proliferation; Cell survival; Cell differentiation