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

Specific knockdown of hippocampal astroglial EphB2 improves synaptic function via inhibition of D-serine secretion in APP/PS1 mice. Am J Transl Res. 2019;11(2):1073-1083 Authors: Qi L, Cui EH, Ji CM, Zhang XB, Wang ZA, Sun YZ, Xu JC, Zhai XF, Chen ZJ, Li J, Zheng JY, Yu RT Abstract 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. PMID: 30899407 [PubMed]
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research

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