Hippocampal alteration of monoaminergic neurotransmitters biosynthesis and metabolism in CNS in rats, after prenatal and postnatal exposure to chlordimeform, through sex hormones disruption
- María José Anadón
- Paula Moyano
- José Manuel García
- María Teresa Frejo
- Miguel Andrés Capó
- Andrea Flores
- Adela Pelayo
- Emma Sola
- Gloria Gómez
- Javier del Pino
ISSN: 2255-0569
Año de publicación: 2017
Volumen: 32
Número: 3
Páginas: 31-39
Tipo: Artículo
Otras publicaciones en: Medicina balear
Resumen
Introduction: Chlordimeform, just as other formamidine pesticides, induces permanent region- and sex-dependent on monoaminergic neurotransmitter systems’ development, effects that may be related to monoamine oxidase (MAO) inhibition. Nevertheless, chlordimeform is a very weak MAO inhibitor, which suggests other mechanisms’ implication. In this regard, as chlordimeform alters testosterone and estradiol levels in frontal cortex and stratium, which may dysregulate the enzymes’ expression that mediates the synthesis and metabolism of monoaminergic neurotransmitters systems. Thus, an alteration of these hormones and enzymes in other altered brain regions could also mediate the observed effects. Objectives and methods: For the purpose of confirming that formamidines produce permanent alterations of monoamine neurotransmitters’ systems through the disruption of sex hormones in the hipoccampus, by alteration of the expression of the enzymes that synthesize and or metabolize these neurotransmitters, hippocampus’ testosterone and estradiol levels 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 (5mg/kg body weight) were evaluated. Results: Our results show an important decrease in testosterone levels, in addition to a significant decrease in estradiol levels in hippocampus of rats at 11 days of age. We also observed sex interaction with treatment in the content of T and E2, and we determined a bigger increase in the expression of COMT in females than in males. Chlordimeform treatment did not alter the expression of MAO and BDH enzymes, yet decreased the expression of the TH enzyme and increased the COMT, BDH, TH and TRH enzymes in both sexes. Conclusions: The present findings indicate that after maternal exposure to formamidines, in general, and chlordimeform, in particular, the previously mentioned compound induces a permanent alteration of monoaminergic neurotransmitters, by the alteration of the enzymes that synthetize these neurotransmitters, which is successively mediated by sex hormones disruption, in hippocampus.