Mechanism of Dabuyuan Jian in Promoting Neurogenesis of Hippocampus in APP/PS1 Double Transgenic Dementia Mice Based on Wnt/β-catenin Signaling Pathway / 中国实验方剂学杂志

ABSTRACT

Objective:To investigate the possible mechanism of Dabuyuan Jian to promote neurogenesis by studying the effect of Dabuyuan Jian on Wnt/β-catenin signaling pathway in hippocampus of amyloid precursor protein/presenilil(APP/PS1) mice. Method:Totally 30 5-month-old APP/PS1 mice and 10 wild mice were divided into control group, model group, donepezil group (6.5×10-4 g·kg-1·d-1) and Dabuyuan Jian group (13.2 g·kg-1·d-1), and given drugs by gavage for 30 days. The control group and the model group were given an equal volume of saline. The learning and memory of mice were evaluated by water maze. The pathological changes of hippocampal neurons were observed by hematoxylin-eosin (HE) staining. The immunohistochemistry (IHC) was used to detect label positive cells of 5-bromodeoxyuridine (Brdu), adrenocortical hormone (Dcx) and neuronal nuclear antigen (NeuN). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western bolt were used to detect the mRNA and protein expression levels of β-catenin and glycogen synthase kinase-3β(GSK-3β) in hippocampus of mice. Result:Compared with the control group, the latency and swimming total distance of the model group were significantly increased (P<0.01), while the number of crossing platforms and the target quadrant time were significantly reduced (P<0.01). Compared with the model group, the platform latency and the total swimming distance of the donepezil group and the Dabuyuan Jian group were decreased (P<0.05, P<0.01), while the number of crossing platforms and the target quadrant time were increased (P<0.05). Compared with the control group, the number of neurons in the hippocampal dentate gyrus (DG) area of the model group was decreased, and necrotic neurons were observed. Compared with the model group, the number of neurons in the hippocampal DG area of the mice in the donepezil group and the Dabuyuan Jian group was increased, while the number of necrotic neurons was decreased. Compared with the control group, the number of positive cells labeled with Brdu, Dcx and NeuN in the hippocampal DG area of the model group was significantly decreased (P<0.01). Compared with the model group, the number of positive cells labeled with Brdu, Dcx and NeuN in the hippocampal DG area of the donepezil group and the Dabuyuan Jian group was increased (P<0.05, P<0.01). Compared with the control group, gene and protein expression levels of β-catenin in the hippocampus of the model group were significantly decreased (P<0.01), whereas gene and protein expression levels of GSK-3β were significantly increased (P<0.01). Compared with the model group, gene and protein expression levels of β-catenin in hippocampus of donepezil group and Dabuyuan Jian group were increased (P<0.05, P<0.01), while gene and protein expression levels of GSK-3β were increased (P<0.05, P<0.01). Conclusion:Dabuyuan Jian could promote hippocampal neurogenesis in APP/PS1 double transgenic mice by regulating Wnt/β-catenin signaling pathway.