RESUMO
2,4-D is a chlorophenoxyherbicide used worldwide. We have studied the morphological alterations of 5-HT neurons and glial cells in the mesencephalic nuclei of adult rats exposed to 2,4-D both perinatally (during pregnancy and lactation) and chronically (during pregnancy, lactation and after weaning) with quantitative methods. Pregnant rats were daily exposed to 70 mg/kg of 2,4-D from gestation day (GD) 16 to post-natal day (PND) 23 through diet. After weaning, pups were assigned to one of two sub-groups: T1 (fed with untreated diet until PND 90) and T2 (maintained with 2,4-D diet until PND 90). Brain sections were immunocytochemically stained using polyclonal anti-5-HT, anti-GFAP and anti-S-100 protein antibodies as cells markers. 2,4-D exposure during pregnancy and lactancy (T1 group) produced an increase in 5-HT neuronal area and immunoreactivity (IR) in the mesencephalic nuclei studied. However, with the chronical 2,4-D exposure (T2 group) only the 5-HT neuronal area from the dorsal raphe nucleus (DRN) was increased, suggesting an adaptable response of 5-HT neurons in median raphe nucleus (MRN). The presence of reactive astrocytes in mesencephalic nuclei and in hippocampus were also different for the two 2,4-D exposure designs, showing the existence of a correspondence between neuronal changes and astrogliosis. Results support evidences that 2,4-D alters the serotoninergic system and that 5-HT neurons of each mesencephalic nuclei show different responses to the 2,4-D exposure designs which are parallel to astrogliosis.
Assuntos
Ácido 2,4-Diclorofenoxiacético/toxicidade , Astrócitos/efeitos dos fármacos , Astrócitos/ultraestrutura , Encéfalo/citologia , Herbicidas/toxicidade , Neurônios/efeitos dos fármacos , Neurônios/ultraestrutura , Serotonina/fisiologia , Animais , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/ultraestrutura , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Indicadores e Reagentes , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Núcleos da Rafe/efeitos dos fármacos , Núcleos da Rafe/patologia , Núcleos da Rafe/ultraestrutura , Ratos , Proteínas S100/metabolismoRESUMO
Neonate rats were exposed to 100 mg/kg from the PND 7 to PND 25 or at 70 mg/kg from PND 12 to PND 25. Treated and control pups were subjected to several behavioral tests (righting reflex, negative geotaxy, forelimbs support and open field) during the period of treatment. At PND 25 the regional effects of 2,4-D on gangliosides composition and myelin deposition were determined. The results indicate that the first design of exposure to 2,4-D produces significant diminutions in body and brain weight from PND 21. Furthermore, these pups showed decrease in GM1 level, diminution in myelin deposition and alterations in all behavioral tests. On the other hand, when treatment was not too severe (minor dose and shorter period of treatment), pups showed alterations in forelimb support and in open field tests without body or brain weight modifications. They also presented diminutions in GM1, mayoritary ganglioside of myelin, and in myelin deposition. These results suggest that in this latter 2,4-D exposure design, undernutrition could not be involved.