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

Author:

Moyano Paula1ORCID,Flores Andrea1ORCID,Fernández María de la Cabeza2,García Jimena1,Sanjuan Javier1,Plaza José Carlos3ORCID,Del Pino Javier1ORCID

Affiliation:

1. Pharmacology and Toxicology Department, Veterinary School, Complutense University, 28040 Madrid, Spain

2. Chemistry in Chemical Sciences Department, Pharmacy School, Complutense University, 28040 Madrid, Spain

3. Legal Medicine, Psychiatry and Pathology Department, Medicine School, Complutense University, 28040 Madrid, Spain

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.

Funder

Santander Bank/UCM

Alborada Foundation/Catedra Extradordinaria de Patologia y Medioambiente

Publisher

MDPI AG

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