Exposição pré-imaginal ao Ferro causa alterações comportamentais similares ao autismo e modula a atividade de enzimas antioxidantes em Drosophila melanogaster

Abstract

Autistic Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by social interaction deficits, learning difficulties, communicative deficits and stereotypy. It is known that about 1 in every 100 children reports this disorder, which persists during all life of the individual. Thus, the description of the etiology of this disorder becomes extremely relevant. Studies demonstrate the contribution of environmental and genetic factors for ASD etiology. It was demonstrated that both Iron (Fe) deficiency or overload during embryonic development are implied in neurodevelopmental disorders. It was also reported that prenatal exposure to high Fe levels is associated with ASD behavioral characteristics in children, such as learning, cognition and locomotion disorders. Oxidative stress results from an unbalance of antioxidant defense and levels of oxidant species leading to cellular damage. Exposure to augmented levels of Fe over gestational period leads to oxidative stress, especially in the brain which is sensitive to the damage induced by free radicals, being implied in several neurological disorders. Thus it becomes important to study the relation between Fe and ASD. The model organism Drosophila melanogaster has brought important contributions for the study of neurological disorders such as ASD. Characteristics like fast reproductive cycle, and genetic similarities of genes related to diseases in humans and a low maintenance cost make this model specially relevant for developmental studies. The present study investigated the Fe toxicity in the D. melanogaster models over the developmental period, taking into consideration factors like oxidative stress and behavioral changes which simulates the autistic-like behavior and are described in the literature for the study of ASD. For this purpose, D. melanogaster was exposed over the developmental cycle until the pupal eclosion to Fe concentrations. Flies up to 5 days old were used for biochemical and behavioral analysis. Fe exposure to 5 and 15 mM concentrations increased lipid peroxidation, and augmented the activity of Superoxide Dismutase whereas decreased Glutathione-S-transferase activity. The flies exposed to Fe displayed a decreased locomotor capacity in the negative geotaxis test, and a prolonged period displaying grooming, which is considered a repetitive behavior, and also an antisocial behavior. Thus, the present study contributes for a better comprehension of factors implied in ASD, and draws attention for Fe toxicity over developmental period, however, further studies are necessary to a better description of this process. Additionally, the use of D. melanogaster for investigation of factors which predisposes to autism was reinforced in this study.