Neural Regeneration Research ›› 2019, Vol. 14 ›› Issue (13): 2400-2407.

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Glutamate receptors delocalization and impairment of hippocampal long-term potentiation precedes local extracellular Aβ deposition in asymptomatic 5XFAD mouse model

Ning Li 2,3,4 , Yang Li 2,3,4 , Lijuan Li 2,3,4 , Ke Zhu 2,3,4 , Yan Zheng 1,3,4, Xiaomin Wang 2,3,4   

  1. 1 Department of Physiology,
    2 Department of Neurobiology,
    3 Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, China.
    4 Beijing Institute for Brain Disorders, Beijing100069, China.
  • Online:2019-12-19
  • Contact: Yan Zheng , zhengyan@ccmu.edu.cn; Xiaomin Wang, xmwang@ccmu.edu.cn
  • Supported by:

    This study was supported by National Natural Science Foundation of China (Yan Zheng, 81571038, 81771145), Projects Under Beijing Municipality (Xiaomin Wang, Z161100002616007).

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Abstract:

Alzheimer disease(AD) is the most common form of dementia. Since the synaptic plasticity is considered the cellular mechanism of memory formation and its impairment is found involve in dementia, it is necessary to clarify the checkpoint of synaptic plasticity decline and associated mechanism in early stage of AD process. Mice at age of 12 weeks were subjected to spatial learning test in Morris water maze. The 6-10 weeks old 5XFAD mice and their age-matched littermates were used to record long-term potentiation (LTP) in dentate gyrus (DG) of hippocampus. In addition, mice at age of 10 weeks were applied in observation of Aβ immunostaining and synaptic subcellular fractionation. Deficit in reversal learning was not developed in the AD mice until 14 weeks old. The impairment of LTP in DG of 5XFAD mice at 10 weeks old occurred, accompanying with synaptic delocalization of AMPA and NMDA receptor subunits. Meanwhile, Aβ was found accumulated intracellularly in hippocampus of the mouse model with no extracellular Aβ deposition. However, no changes in basal synaptic transmission in hippocampus of these AD mice compared to wild type control were detected. The delocalization of postsynaptic glutamate receptors and its associated decline in synaptic plasticity may be a leading event within the AD pathological context, even preceding the senile plaque formation in the 5XFAD mouse model. This study provides a referable checkpoint for studying pathogenesis of AD.