Sex differences and effects of estrogenic compounds on the expression of inflammatory molecules by astrocytes exposed to the insecticide dimethoate

Abstract

A low dose of the organophosphorus insecticide dimethoate (DMT) produces oxidation of lipids and proteins and impairs mitochondrial function in the brain of male rats, together with a reduction of gonadal hormones in plasma. Here, we have assessed whether DMT affected the expression of inflammatory molecules, the production of reactive oxygen species (ROS), and the expression of steroidogenic proteins and estrogen receptors in cortical astrocyte-enriched cultures obtained separately from male and female CD1 mice pups. Furthermore, we have analyzed whether estradiol may counteract the effects of DMT. A dose of DMT (2 μg/mL) did not affect cell viability, increased interleukin (IL) 6, IL1β, tumor necrosis factor (TNF)α, interferon-γ-inducible protein 10 (IP10), ERβ, steroidogenic acute regulatory protein, and aromatase mRNA levels and ERα protein levels in male but not in female cultures. Estradiol decreased the mRNA levels of IL6, IP10, TNFα, and IL1β in male but not in female cultures treated with DMT. The effect of estradiol was prevented by the ER antagonist ICI 182,780, fully imitated by an ERβ agonist and partially imitated by an ERα agonist. Furthermore, DMT increased the production of ROS in male astrocytes while estradiol reduced ROS production to control levels. These findings indicate that a sublethal dose of DMT alters astrocyte function. The selective action of estradiol on male astrocytes and the sexually dimorphic action of DMT suggest that the pesticide may have different neurological outcomes in males and females.