Sex differences and effects of estrogenic compounds on the inflammatory response of astrocytes exposed to the insecticide dimethoate

ACAZ-FONSECA, ESTEFANIA; GARCIA-SEGURA, LUIS M; ASTIZ, MARIANA

Torino

Congreso; 7th International Meeting Steroids and Nervous System; 2013

University of Torino, Italy

Dimethoate (DMT) is an organophosphorous (OP) insecticide extensively used in horticulture for pest treatment and as an acaricide for treating gardens, vineyards, and field crops. A low dose of the DMT results in high oxidation of lipids and proteins and in impairment of 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 inflammatory response, the production of reactive oxygen species (ROS) and the expression of steroidogenic proteins and estrogen receptors (ERs) 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 (2μg/mL) that did not affect cell viability increased the mRNA levels of interleukin (IL) 6, interferon-gamma-inducible protein 10 (IP10), tumor necrosis factor (TNF) alpha, IL1beta, ERalpha, ERbeta, steroidogenic acute regulatory protein (StAR) and aromatase in male but not in female cultures. Estradiol decreased the mRNA levels of IL6, IP10, TNFalpha, and IL1beta 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 ERbeta agonist and partially imitated by an ERalpha 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 antiinflammatory 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.