Striatal alteration of monoaminergic neurotransmitters systems in rats, after prenatal and postnatal exposure to chlordimeform, through testosterone and estradiol disruption

Abstract

Introduction: Chlordimeform, as well as other formamidine pesticides, induce permanent sex- and region-dependent effects on development of monoaminergic neurotransmitter systems. These effects could be related to monoamine oxidase (MAO) inhibition. However, chlordimeform is a very weak MAO inhibitor, which suggest that other mechanism should be involved. In this regard, chlordimeform alters testosterone and estradiol levels in frontal cortex, which lead to a disruption of the enzymes’ expression that mediate the synthesis and metabolism of monoaminergic neurotransmitters systems. Therefore, an alteration of these hormones and enzymes in the other brain regions altered could also mediate the effects observed. Objectives and methods: In order to confirm that the formamidines produce permanent alterations of the monoamine neurotransmitter systems, through disruption of sex hormones in the striatum, by alteration of the expression of the enzymes that synthesize and/or metabolize these neurotransmitters, we evaluated, in striatum of male and female rats, the effect on the levels of testosterone and estradiol at 11 days of age, as well as the expression of MAO, COMT, BDH, TH, TRH, and AD enzymes at 60 days of age after maternal exposure to chlordimeform (5 mg / kg body weight). Results: Chlordimeform induced a significant decrease in testosterone and estradiol levels in striatum of rats at 11 days of age. We observed sex interaction with treatment in the content of T and E2. We determined a bigger increase in the expression of BDH [44,65% (P<0,001)] enzyme in females than in males. Chlordimeform treatment did not alter the expression of MAO and AD enzymes, but decreased the expression of the enzymes COMT, BDH, TH and TRH in both males and females. Conclusions: The present findings indicate that after maternal exposure to formamidines, in general, and chlordimeform, in particular, a permanent alteration of monoaminergic neurotransmitters, through alteration of the enzymes that synthetize these neurotransmitters, mediated by sex hormones disruption, in striatum, is induced.