Diazinon and diazoxon impair the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons

Toxicology and Applied Pharmacology
Daniella PizzurroLucio G Costa

Abstract

Evidence from in vivo and epidemiological studies suggests that organophosphorus insecticides (OPs) are developmental neurotoxicants, but possible underlying mechanisms are still unclear. Astrocytes are increasingly recognized for their active role in normal neuronal development. This study sought to investigate whether the widely-used OP diazinon (DZ), and its oxygen metabolite diazoxon (DZO), would affect glial-neuronal interactions as a potential mechanism of developmental neurotoxicity. Specifically, we investigated the effects of DZ and DZO on the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons. The results show that both DZ and DZO adversely affect astrocyte function, resulting in inhibited neurite outgrowth in hippocampal neurons. This effect appears to be mediated by oxidative stress, as indicated by OP-induced increased reactive oxygen species production in astrocytes and prevention of neurite outgrowth inhibition by antioxidants. The concentrations of OPs were devoid of cytotoxicity, and cause limited acetylcholinesterase inhibition in astrocytes (18 and 25% for DZ and DZO, respectively). Among astrocytic neuritogenic factors, the most important one is the extracellular matrix protein ...Continue Reading

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Citations

Jan 23, 2016·Frontiers in Integrative Neuroscience·Clare J Wilhelm, Marina Guizzetti
Nov 27, 2014·Frontiers in Pediatrics·Marina GuizzettiDavid P Gavin
Nov 9, 2016·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Zhenwei LiJing Shao
Feb 6, 2017·Frontiers in Neuroscience·Jaymie R VoorheesAndrew A Pieper

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