L-3-n-butylphthalide Promotes Adult Neurogenesis Through BDNF Signal Pathway And Neural Progenitors Cell Proliferation

Objectives Adult neurogenesis, especially adult hippocampal neurogenesis are closely linked to learning and memory. The L-3-n-butylphthalide (NBP) as a common clinical drug to moderate ischemic stroke, improve cognitive effects, which improves cognitive function in patients with stroke mechanism may be related to adult neurogenesis in the dentate gyrus. We intended to explore the effects of NBP on cognitive improvement and neurogenic enhancement and the possible underlying mechanisms in rat model with different concentrations of NBP.Methods Animal level:The animals were divided into the Sham group, the bilateral common carotid artery occlusion (2VO) group, the NBP intervention group, in which rat were administered orally by gastric intubation of different concentrations of NBP (30,60,120mg/kg) for four consecutive weeks, and the 2VO+NBP (120mg/kg) +K252a group. In this study, the spatial memory and learning ability were tested by the water maze.5-bromo-2'-deoxyuridine (BrdU) and BrdU/neuronal nuclei (NeuN) immunohistological staining was performed to investigate the impact of NBP on the proliferation. Using rt-PCR and Western Blot to analyze the expression level of BDNF, ERK and CERB of hippocampal tissue in rats in different group.Results The results indicate that NBP can improve spatial memory and cognitive learning ability in rats. And NBP can promote adult neurogenesis, but has no effect on differentiation in vivo. NBP can increase BDNF, pERK and pCERB expression levels in dose-dependent manner, the effect can be suppressed by BDNF inhibitor K252a.Conclusion NBP can improve spatial memory and cognitive levels in rats, this effect is closely related to the occurrence of adult neurogenesis, and its promotion of adult neurogenesis may be due to increased BDNF, pERK and pCERB expression levels.