Dabuyuan Jian Improves Hippocampal Synaptic Plasticity of APP/PS1 Double Transgenic Mice by Regulating BDNF/TrkB/CREB Signal Pathway / 中国实验方剂学杂志

ABSTRACT

Objective:To observe the effect of Dabuyuan Jian on the synaptic plasticity of hippocampus and the brain derived neurotrophic factor （BDNF）/tyrosine kinase receptor （TrkB）/cyclic adenosine phosphate reactive element binding protein （CREB） signaling pathway in amyloid precursor protein/presenilil （APP/PS1） mice， and to explore its possible mechanism for improving synaptic plasticity. Method:Totally 36 APP/PS1 mice were divided into 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 another wild mice were set as control group. The mice in control group and model group received an equal volume of saline， and the mice in each group received drugs by gavage for 30 days. The learning ability and memory of mice in each group were detected by Morris water maze. The pathological changes of neurons and synapses in the hippocampus of each group were observed by Nissl staining and Golgi staining. The expression levels of postsynaptic density protein 95 （PSD95） and synaptophysin （SYN） in hippocampus of each group were detected by immunofluorescence （IF）. The protein expression levels of BDNF， TrkB， CREB and phosphorylated CREB （p-CREB） in hippocampus were detected by Western blot. Result:As compared with the control group， the platform latency and total swimming distance of the model group were increased in the model group （P<0.01）， with decreased times of crossing the platform and staying time in the target quadrant （P<0.01）， the intracellular Nissl bodies of neurons in hippocampal CA3 area decreased or disappeared in model group， with decreased number of neurons and dendritic branches and decreased density of dendritic spine in hippocampal CA3 area of the mice （P<0.01）， and the protein expression levels of SYN， PSD95， BDNF， TrkB and p-CREB in hippocampus of mice were also decreased in model group （P<0.05， P<0.01）. As compared with the model group， the platform latency and total swimming distance were decreased in the donepezil group and Dabuyuan Jian group （P<0.05， P<0.01）， with increased times of crossing platform and staying time in target quadrant （P<0.05， P<0.01）， the number of Nissl bodies of neurons in hippocampal CA3 area was increased in the donepezil group and Dabuyuan Jian group， with increased number of neurons and dendritic branches and increased density of dendritic spine in hippocampal CA3 area of the mice， and the protein expression levels of SYN， PSD95， BDNF， TrkB and p-CREB in hippocampus of mice were increased in the donepezil group and Dabuyuan Jian group （P<0.05， P<0.01）. Conclusion:Dabuyuan Jian can improve the synaptic plasticity of APP/PS1 double transgenic mice， and its mechanism may be related to its up-regulation of BDNF/TrkB/CREB signal pathway in mouse hippocampus.