Effect of aerobic exercise on BDNF/proBDNF expression in the ischemic hippocampus and depression recovery of rats after stroke

Abstract

BDNF and proBDNF play an opposite role in hippocampal neurogenesis. What remains to be known is the effect of balance between BDNF and proBDNF in the ischemic hippocampus on pathogenesis of post-stroke depression (PSD) and the potential mechanisms of aerobic exercise (AE) on PSD. Wistar rats were randomly divided into control, Sham, Sedentary and AE groups. After PSD model was successful made, the blood lactate threshold corresponding speed (S_LT) were measured. The behavioral tests (open field, forced swimming and sucrose preference tests) were performed before and after 4 weeks of aerobic treadmill training. HE staining and immunostaining for doublecortin (DCX)⁺ neurons were used to observe the changes of neuronal cell morphology and proliferation, migration of the neural progenitor cells (NPCs). The expression of mature brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), precursor BDNF (proBDNF), pan-neurotrophin receptor 75 (p75NTR) proteins, BDNF mRNA in the ischemic hippocampus and serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were detected by Western blotting, immunohistochemistry, RT-PCR and ELISA. Higher immobility time and levels of proBDNF, p75NTR, ACTH, CORT proteins and lower sucrose preference, total distance, climbing frequency and levels of BDNF, TrkB proteins, BDNF mRNA were observed in the Sedentary group. Neuronal cells in the ischemic hippocampus were loosely arranged and expression of DCX reduced in the Sedentary group. There were significant differences in above results between Sedentary and AE groups after 4 weeks of aerobic exercise. The balance between BDNF and proBDNF in the ischemic hippocampus are likely to play an important role in the pathogenesis of PSD. And AE could improve depression, hippocampal neurogenesis, and increase BDNF/proBDNF ratio in the ischemic hippocampus of the PSD rats.

Keywords: Depression; Exercise; Hippocampus; Neurogenesis; Stroke.