Increased Levels of Phosphorylated-P38α Induce WNT/β-Catenin and NGF/P75NTR/TrkA Pathways Disruption and SN56 Cell Death following Single and Repeated Chlorpyrifos Treatment

单次和重复使用毒死蜱处理后,磷酸化 P38α 水平升高会诱导 WNT/β-Catenin 和 NGF/P75NTR/TrkA 通路中断和 SN56 细胞死亡

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作者:Paula Moyano, Andrea Flores, María de la Cabeza Fernández, Jimena García, Javier Sanjuan, José Carlos Plaza, Javier Del Pino

Abstract

Chlorpyrifos (CPF) biocide, exposure to which is mainly produced in the human population through diet, induces several neurotoxic effects. CPF single and repeated exposure induces memory and learning disorders, although the mechanisms that produce these outcomes are complex and not well understood. CPF treatment (single and repeated) of cholinergic septal SN56 cells induced an increase in phosphorylated-P38α levels that led to WNT/β-Catenin and NGF/P75NTR/TrkA pathways disruption and cell death. These results provide new knowledge on the mechanisms that mediate CPF basal forebrain cholinergic neuronal loss induced by CPF single and repeated exposure and can help unravel the way through which this compound produces cognitive decline and develop efficient treatments against these effects.

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