Developmental exposure to mancozeb induced neurochemical and morphological alterations in adult male mouse hypothalamus.

Mancozeb, a dithiocarbamate widely used in agriculture, is considered a developmental hazard in humans; however, more evidences are still needed concerning the consequences of chronic exposure to this pesticide. Mancozeb neurotoxicity in developing mouse hypothalamus was evaluated by subchronic exposure of male Mus musculus mice to low and high doses of mancozeb (30 and 90 mg/kg body weight, respectively) from late neonatal until adolescence. Variations in hypothalamic amino acid neurotransmitter levels and changes in histological as well as cytological characteristics were analyzed in young adult experimental mice and compared with control. A dose-dependent increase in excitation/ inhibition ratio was observed in mancozeb-exposed hypothalamus, indicating an overall state of excitoxicity. Histopathological and ultrastructural studies showed increased apoptosis, neuroinflammation and demyelination, demonstrating mancozeb-induced cytotoxicity in hypothalamic neurosecretory cells. In summary, both neurochemical and morphological data revealed mancozeb-induced alterations during development of hypothalamic circuitry that are critical for maturation of the neuroendocrine system.

Neurotoxicidad de los plaguicidas como agentes disruptores endocrinos: una revisión / Neurotoxicity of pesticides as endocrine disruptors agents: a review

Los plaguicidas se encuentran en el medio ambiente como contaminantes formando mezclas complejas, los estudios recientes se han centrados en la evaluación de los efectos y riesgos que pueden causar estas mezclas de plaguicidas en el ser humano y los ecosistemas.Esta revisión hace hincapié a tres plaguicidas específicos, representativos de los grupos químicos organofosforados, carbamato de tipo ditiocarbamato y triazinas, como son: Paratión® etílico, Mancozeb® y Atrazina®, respectivamente. Ha sido demostrado en animales de experimentación la neurotoxicidad de estos plaguicidas por alteración de la transmisión sináptica y de los mecanismos de la homeostasis del sistema neuroendocrino, lo cual explica la acción de estos plaguicidas como disruptores endocrinos. Varios trabajos demuestran que estos plaguicidas son potencialmente tóxicos a la salud humana, y aún en bajas concentraciones, pueden afectar al organismo causando alteraciones en el sistema neuroendocrino, especialmente en los ejes hipotálamo-hipófisis-gónada e hipotálamo-hipófisis-tiroides. Los investigadores destacan que los momentos de particular sensibilidad de la exposición a plaguicidas disruptores endocrinos son las etapas tempranas de la vida como: durante el desarrollo embrionario y la primera infancia, períodos en los cuales los procesos de crecimiento son controlados por las hormonas afectando el desarrollo del cerebro, el sistema inmune y otros órganos como el sistema reproductor y tiroideo. Los cambios neuroquímicos provocados por la exposición a estos plaguicidas durante el desarrollo cerebral constituyen un alto riesgo porque son capaces de interferir en los procesos de neurogénesis y sinaptogénesis, afectando de manera adversa las funciones cognitivas y motoras, cuyos efectos se observan durante las etapas posteriores de la vida.

Pesticides are found in the environment as complex mixtures forming pollutants, recent studies have focused on evaluating the effects and risks that may cause these mixtures of pesticides on humans and ecosystems. This review highlights three specific, representative of organophosphorus pesticide chemical groups carbamate, dithiocarbamate and triazine type, such as: ethyl Paratión®, Mancozeb® and Atrazina®, respectively.It has been demonstrated in experimental animal’s neurotoxicity of these pesticides by altering synaptic transmission and mechanisms of homeostasis of the neuroendocrine system, which explains the action of these pesticides as endocrine disruptors. Several studies show that these pesticides are potentially toxic to human health, and even in low concentrations, can affect the body causing alterations in the neuroendocrine system, especially in the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroid axis. The researchers point out that the moments of particular sensitivity of exposure Endocrine disruptor pesticide are the early stages of life as during embryonic development and early childhood periods in which growth processes are controlled by hormones affecting the development brain, immune system and other organs such as the thyroid and reproductive system. The neurochemical changes induced by exposure to these pesticides during brain development are at high risk because they are able to interfere with the processes of neurogenesis and synaptogenesis, adversely affecting cognitive and motor functions, whose effects are observed during the later stages of life.