Specific knockdown of hippocampal astroglial EphB2 improves synaptic function via inhibition of D-serine secretion in APP/PS1 mice

American Journal of Translational Research

En-Hui Cui¹  Chun-Mei Ji²  Xiao-Bing Zhang³  Liang Qi⁴ 

[1] Department of Anesthesiology, Huaian Matenal and Child Health Hospital, Huaian, Jiangsu, China;Department of Neurosurgery, Huaian Second Peoples Hospital and The Affiliated Huaian Hospital of Xuzhou Medical University, Huaian, Jiangsu, China;Laboratory of Neurosurgery, Xuzhou Medical University, Xuzhou, Jiangsu, China;Xuzhou Medical University, Xuzhou, Jiangsu, China

关键词: Alzheimer’;    s disease;    astrocyte;    D-serine;    EphB;    synaptic plasticity;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Increasing evidence emphasizes the protective role of Eph receptors in synaptic function in the pathological development of Alzheimer’s disease (AD); however, their roles in the regulation of hippocampal astrocytes remain largely unknown. Here, we directly investigated the function of astroglial EphB2 on synaptic plasticity in APP/PS1 mice. Using cell isolation and transgene technologies, we first isolated hippocampal astrocytes and evaluated the expression levels of ephrinB ligands and EphB receptors. Then, we stereotaxically injected EphB2-Flox-AAV into the hippocampus of GFAP-cre/APP/PS1 mice and further evaluated hippocampal synaptic plasticity and astroglial function. Interestingly, astrocytic EphB2 expression was significantly increased in APP/PS1 mice in contrast to its expression profile in neurons. Moreover, depressing this astroglial EphB2 upregulation enhanced hippocampal synaptic plasticity, which results from harmful D-serine release. These results provide evidence of the different expression profiles and function of EphB2 between astrocytes and neurons in AD pathology.

【 授权许可】

CC BY-NC