PRG-1 prevents neonatal stimuli-induced persistent hyperalgesia and memory dysfunction via NSF/Glu/GluR2 signaling
Xingfeng Liu, Site Li, Wenyu Zhang, Zhuo Xie, Jingxin He, Xuanwei Zhang, Shouyang Yu, Song Cao, Tian Yu, Zhi Xiao
Journal：iScience
IF：6.11
DOI：10.1016/j.isci.2022.104989
PMID：36093041
Published：2022-08-24
research field：分子生物学细胞信号传导风湿病学药理学天然产物研究
Abstract
Summary Neonatal repetitive noxious stimuli (RNS) has been shown to cause long-term harmful effects on nociceptive processing, learning, and memory which persist until adulthood. Plasticity-related gene 1 (PRG-1) regulates synaptic plasticity and functional reorganization in the brain during neuronal development. In this study, neonatal RNS rats were established by repetitive needle pricks to neonatal rats on all four feet to model repetitive pain exposure in infants. Neonatal RNS caused thermal hyperalgesia, mechanical allodynia, learning, and memory impairments which manifested in young rats and persisted until adulthood. Hippocampal PRG-1/N-ethylmaleimide sensitive fusion protein (NSF) interaction was determined to be responsible for the RNS-induced impairment via enhanced extracellular glutamate release and AMPAR GluR2 trafficking deficiency in a cell-autonomous manner. These pathways likely act synergistically to cause changes in dendritic spine density. Our findings suggest that PRG-1 prevents the RNS-induced hyperalgesia, learning, and memory impairment by regulating synaptic plasticity via NSF/Glu/GluR2 signaling.
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