Overexpression of human wtTDP-43 causes impairment in hippocampal plasticity and behavioral deficits in CAMKII-tTa transgenic mouse model.

Zainuddin Quadri,Nicholas Johnson,Frank Zamudio,Abrian Miller,Melinda Peters,Shayna Smeltzer,Jerry B Hunt,Steven B Housley,Breanna Brown,Susan Kramer,Christopher M Norris,Kevin Nash,Edwin Weeber,Daniel C Lee,Maj-Linda B Selenica

Molecular and Cellular Neuroscience（2020）

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摘要

•We report a novel role of human wtTDP-43 and alpha synuclein in hippocampal biology and neurodegenerative disorders.•AAV-overexpression of wtTDP-43 contributes to CA2–specific pyramidal neuronal loss and reduced hippocampal volume.•We identified thatwtTDP-43 induced selective degeneration of Purkinje Cell Protein 4 (PCP-4) positive neurons in the CA2.•Overexpression of both human wtTDP-43 and alpha synuclein significantly decreased hippocampal glutamate receptors GluR1/R2 expression.

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关键词

FTLD,ALS,TDP-43,α-Synuclein,PCP-4,Glutamate receptor,CA2,Hippocampus,Synaptic plasticity,Learning

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