Effects of Qingxin Kaiqiao Formula(清心开窍方)on Learning and Memory Ability of APP/PS1 Double Transgenic Mice Based on BDNF/TrkB Pathway
Objective To investigate the effects of Qingxin Kaiqiao Formula(清心开窍方)on cognitive function and neuronal protection in amyloid precursor protein(APP)/presenilin-1(PS1)double transgenic mice based on brain-derived neurotrophic factor(BDNF)/tropomyosin-related kinase B(TrkB)pathway.Methods Thirty APP/PS1 mice were divided into the model group,Aricept group(1.67 mg·kg-1·d-1),Qingxin Kaiqiao Formula low dose group(4.75 mg·kg-1·d-1),Qingxin Kaiqiao Formula medium dose group(9.5 mg·kg-1·d-1)and Qingxin Kaiqiao Formula high dose group(19 mg·kg-1·d-1)according to the random number table method.Six male C57/B6 mice were selected as the control group and given the drugs by gavage at 9:00 am daily for 90 days.After gavage,the spatial learning memory of the mice was tested by Morris water maze.The cell morphological changes in the CA1 region of the hippocampus were observed by HE staining.The pathological morphological changes in the CA1 region of the hippocampus were observed by Nissl staining.The expressions of TrkB,β amyloid precursor protein lyase 1(BACE1)and BDNF mRNA in the hippocampus of the mice wre detected by real-time fluorescence quantitative polymerase chain reaction(Real-time qPCR).The expression levels of protein P-TrkB,TrkB,BACE1 and BDNF proteins were detected by protein immunoblotting(Western blotting,WB).Results Compared with those in the control group,the mice in the model group showed a significantly higher escape latency(P＜0.01),a significantly higher number of platform crossings and a significantly longer retention time in the quadrant of the original platform(P＜0.01),severe damage to hippocampal neurons,loo-ser arrangement,reduced number of nisomes,lighter staining,increased expression of BACE1(P＜0.01)and decreased expres-sions of P-TrkB,TrkB and BDNF expression(P＜0.01).Compared with the model group,the Qingxin Kaiqiao Formula treat-ment groups had a shorter escape latency,a significantly higher number of crossing platforms and a longer dwell time in the target quadrant(P＜0.05 or P＜0.01),a tighter arrangement of hippocampal pyramidal cells,an intact morphology,an increase in the number of nisomes,a deeper coloration,a lower expression of BACE1(P＜0.05 or P＜0.01)and increased expressions of P-TrkB,TrkB and BDNF(P＜0.05 or P＜0.01).Conclusion Qingxin Kaiqiao Formula may improve the learning memory ability of APP/PS1 mice through the BDNF/TrkB pathway and plays a protective role on neural cells.
万方数据
维普
