Neural Regeneration Research ›› 2019, Vol. 14 ›› Issue (6): 1037-1045.doi: 10.4103/1673-5374.250625

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Glutamate receptor delocalization in postsynaptic membrane and reduced hippocampal synaptic plasticity in the early stage of Alzheimer’s disease

Ning Li 1, 2, 3 , Yang Li 1, 2, 3 , Li-Juan Li 2, 3, 4 , Ke Zhu 2, 3, 4 , Yan Zheng 2, 3, 4 , Xiao-Min Wang 1, 2, 3   

  1. 1 Department of Neurobiology, Capital Medical University, Beijing, China
    2 Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing, China
    3 Beijing Institute for Brain Disorders, Beijing, China
    4 Department of Physiology, Capital Medical University, Beijing, China
  • Online:2019-06-15 Published:2019-06-15
  • Contact: Yan Zheng, PhD, zhengyan@ccmu.edu.cn; Xiao-Min Wang, PhD, xmwang@ccmu.edu.cn.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81571038 , 81771145 (both to YZ).

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Abstract:

Mounting evidence suggests that synaptic plasticity provides the cellular biological basis of learning and memory, and plasticity deficits play a key role in dementia caused by Alzheimer’s disease. However, the mechanisms by which synaptic dysfunction contributes to the pathogenesis of Alzheimer’s disease remain unclear. In the present study, Alzheimer’s disease transgenic mice were used to determine the relationship between decreased hippocampal synaptic plasticity and pathological changes and cognitive-behavioral deterioration, as well as possible mechanisms underlying decreased synaptic plasticity in the early stages of Alzheimer’s disease-like diseases. APP/PS1 double transgenic (5XFAD; Jackson Laboratory) mice and their littermates (wild-type, controls) were used in this study. Additional 6-week-old and 10-week-old 5XFAD mice and wild-type mice were used for electrophysiological recording of hippocampal dentate gyrus. For 10-week-old 5XFAD mice and wild-type mice, the left hippocampus was used for electrophysiological recording, and the right hippocam¬pus was used for biochemical experiments or immunohistochemical staining to observe synaptophysin levels and amyloid beta deposition levels. The results revealed that, compared with wild-type mice, 6-week-old 5XFAD mice exhibited unaltered long-term potentiation in the hippocampal dentate gyrus. Another set of 5XFAD mice began to show attenuation at the age of 10 weeks, and a large quantity of amyloid beta protein was accumulated in hippocampal cells. The location of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor and N-methyl-D-aspartic acid receptor subunits in synaptosomes was decreased. These findings indicate that the delocalization of postsynaptic glutamate receptors and an associated decline in synaptic plasticity may be key mechanisms in the early onset of Alzheimer’s disease. The use and care of animals were in strict accordance with the ethical standards of the animal ethics committee of the Capital Medical Univer¬sity, China on December 17, 2015 (ethics No. AEEI-2015-182).

Key words: nerve regeneration, Alzheimer’s disease, synaptic plasticity, hippocampus, learning and memory, long-term potentiation, &beta, amyloid, glutamate receptor, synaptic strength, neural regeneration