Drosophila melanogaster: um modelo alternativo para o estudo dos efeitos bioquímicos e comportamentais causados pela exposição ao manganês durante o desenvolvimento embrionário

Abstract

Manganese (Mn) is an essential element for humans. It is absorbed through the diet, and the rate of absorption is homeostaticaly controlled by biliary excretion; or inhalation. Exposure to the metal during embryonic development and childhood phases are associated with cognitive deficits and hyperactive behaviors. These periods are particularly critical once occurs a higher metal absorption. The present study aimed to identify biochemical and behavioral alterations in Drosophila melanogaster caused by Mn-exposure during the period of embryonic development. Fruit flies D. Melanogaster were treated with manganese chloride (MnCl2) at concentrations 0.1mM, 0.5mM and 1mM over the developmental period. After eclosion, the flies were used in biochemical and behavior assays and for metal content determination. At 0.5mM and 1mM concentrations, the flies were significantly faster than the control group (p<0.005), evaluated by Negative Geotaxis assay, besides, they exhibited an improvement in Mn levels (p<0.0001) while than a decreasing in Ca, Fe, Cu, Zn and S levels. Cell viability decreased at 1mM group whereas there was an improvement in reactive oxygen species production evaluated by DCF-DA assay, in 0.5mM and 1mM groups (p<0.05). Expression of cellular stress responsive genes was investigated by the real time PCR assay. At 1mM Mn increased the mRNA CAT, SOD (p<0.005) and HSP83 (p<0.0001) expression. On the other hand, catalase and superoxide dismutase enzyme activity was not altered at 0.5 and 1mM groups, while that a significant increasing in thioredoxin reductase (p<0.05) and glutatione-Stransferase (p<0.005 and 0.0001, respectively) enzymes activity were observed. Concerning the phosphorylation of MAPK signaling pathway, Mn treatment did not alter ERK and JNK phosphorylation, but at 1mM an inhibition on p38MAPK phosphorylation occurred. Our results indicate a possible adaptive response to Mn intoxication in D. melanogaster represented by an enhancement in antioxidant defenses and inhibition of signaling pathways associated with apoptotic process. An unbalance of essential metals homeostasis, associated with an improved locomotor activity was observed which could be associated with hyperactive activity reported for children.