Permanent effects on monoaminergic neurotransmitters biosynthesis and metabolism after prenatal and postnatal exposure to Chlordimeform, in female and male rat’s prefrontal cortex

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Javier Del Pino, Paula Moyano, Jose Manuel Garcia, Maria Jesus Diaz, Gloria Gomez, Maria Jose Anadón, Margarita Lobo, Jimena Garcia,
Matilde Ruiz and Maria Teresa Frejo

Complutense University, Spain
Alfonso X University, Spain

: J Forensic Toxicol Pharmacol

Abstract

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Formamidine pesticides induce permanent sex and region-dependent effects on development of monoaminergic neurotransmitter systems. The mechanisms that induce these effects are not known, but it has been suggested that these effects could be related to monoamine oxidase (MAO) inhibition. However, chlordimeform, a formamidine pesticide, is a very weak MAO inhibitor, which suggests that other mechanism should be involved. In this regard, formamidines, in general and chlordimeform, in particular, may alter the expression of the enzymes that mediate the synthesis and metabolism of monoaminergic neurotransmitters systems. Therefore, an alteration of these enzymes in the brain could mediate the effects observed. In order to confirm that the formamidines produce permanent alterations of the monoamine neurotransmitter systems by alteration of the expression of the enzymes that synthesize and/or metabolize these neurotransmitters, we evaluated, in frontal cortex of male and female rats, the effect on 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). Chlordimeform induced a significant decrease in the expression of the enzymes TRH and TH in both males and females. We determined a bigger increase in the expression of TH [35, 66% (P<0,001)] and TRH [42, 14% (P<0,001)] enzymes in males than in females. Chlordimeform treatment did not alter the expression of MAO, COMT, AD, BDH enzymes. The present findings indicate that after maternal exposure to formamidines, in general and chlordimeform, in particular, induces a permanent alteration of monoaminergic neurotransmitters, through alteration of the enzymes that synthetize these neurotransmitters.

Biography

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Javier Del Pino has received his PharmD degree at the University Complutense University of Madrid in 2004. He has specialized in Neurotoxicology and Neurodevelopmental Toxicology and received his PhD in Toxicology in 2009. In 2010, he has worked in Institute of Health Carlos III in the National Center of Environmental Health. From 2010 to 2012, he was an Associate Researcher at University of Massachusetts (UMASS) working in Sandra Petersen´s Lab in a National Institute of Health (NIH) project on developmental effects of TCDD endocrine disruptor on sexual differentiation. In 2016, he became Associate Professor of Toxicology at the Complutense University of Madrid, Spain.

Email: jdelpino@pdi.ucm.es