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amyloid β-protein differentially affects NMDA receptor-and GAbAA receptor-mediated currents in rat hippocampal CA1 neurons

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Progress in Natural Science:Materials International 2009年第8期19卷 963-972页

作者： Junfang Zhanga, Lei Houb, Xiuping Gao a, Fen Guoa, Wei Jingc, Jinshun Qia, Jiantian Qiaoa a Department of Neurobiology, Shanxi Medical University, Taiyuan 030001, China b Anesthesiology Department, Shanxi Tumor Hospital, Taiyuan 030013, China c Department of biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China Department of Neurobiology Shanxi Medical University Taiyuan 030001 China Anesthesiology Department Shanxi Tumor Hospital Taiyuan 030013 China Department of biomedical Engineering Shanghai Jiao Tong University Shanghai 200240 China

Although the aggregated amyloid b-protein (Ab) in senile plaques is one of the key neuropathological features of Alzheimer’s disease (AD), soluble forms of Ab also interfere with synaptic plasticity at the early stage of AD. The suppressive action of acute application of Ab on hippocampal long-term potentiation (LTP) has been reported widely, whereas the mechanism underlying the effects of Ab is still mostly unknown. The present study, using the whole-cell patch clamp technique, investigated the effects of Ab fragments (Ab25–35 and Ab31–35) on the LTP induction-related postsynaptic ligand-gated channel currents in isolated hippocampal CA1 neurons. The results showed a rapid but opposite action of both peptides on excitatory and inhibitory receptor currents. Glutamate application-induced currents weresuppressed by Ab25–35in a dose-dependent manner,andfurtherN-methyl-D-aspartate(NMDA)receptor-mediated currents were selectively inhibited. In contrast, pretreatment with Ab fragments potentiated c-aminobutyric acid (GAbA)-induced whole-cell currents. As a control, Ab35–31, the reversed sequence of Ab31–35, showed no effect on the currents induced by glutamate, NMDA or GAbA. These results may partly explain the impaired effects of Ab on hippocampal LTP, and suggest that the functional down-regulation of NMDA receptors and up-regulation of GAbAA receptors may play an important role in remodeling the hippocampal synaptic plasticity in early AD.

关键词： amyloid b-protein Glutamate-induced current GAbA-induced current Whole-cell patch clamp Hippocampus

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Effect of the electro-acupuncture on senile plaques and its formation in APPD/PS1D double transgenic mice

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Genes & Diseases 2019年第3期6卷 282-289页

作者： Qinghua Yang Shujuan Zhu Jin Xu Chenglin Tang Kaihui Wu Yanjun Wu Yiying Wang Huajun Sheng Institute of Neuroscience Chongqing Medical UniversityChongqingChina College of Traditional Chinese Medicine Chongqing Medical UniversityChongqingChina

Alzheimer’s disease(AD)is a progressive neurodegenerative disease and its incidence will increase with age and is *** senile plaques(SPs)are one of three main pathological features in AD patients,which are formed by amyloid b-protein(Ab)overaccumulation.b-amyloid precursor protein(APP),b-site APP cleavage(bACE1),and insulin degrading enzyme(IDE)proteins participate in the process of Ab production and *** present,the pathogenesis of AD is not yet clear and the current treatment methods can only relief the related symptoms of *** electro-acupuncture(EA)is a traditional Chinese medicine treatment combined the acupuncture and electrical stimulation and the treatment effect can also be controlled by transform the electrical ***,in this experiment,we carried out behavioral test,immunohistochemistry(IHC),and Western blot(Wb)after different period treatments to the model mice by electro-acupuncturing“baihui”and“Shenshu”acupoints in APPt/PS1t double transgenic *** was found that the EA therapy can improve the ability of learning,memory and spatial exploration,and reduce the deposition of SPs in brain of AD model mice,and reduce the expressions of APP and bACE1,increase the expression of IDE *** results prompt that EA can effectively alleviate the pathological process of *** speculate that EA may play a comprehensive role in preventing the development of AD,considering the previous data.

关键词： Alzheimer’s disease amyloid b-protein Electro-acupuncture Senile plaques Transgenic mice

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