RESUMO
Environmental factors are involved in the pathogenesis of neurodevelopmental disorders in addition to genetic factors. In this sense, we demonstrated here that the embryonic exposure of Drosophila melanogaster to Bisphenol A (BPA) 1 mM resulted in changes in development, behavior, and biochemical markers punctuated below. BPA did not alter the oviposition and viability of the eggs, however, it was evidenced a decrease in the rate of pupal eclosion and life span of the hatched flies of the generation filial 1 (F1). F1 flies also developed behavioral changes such as incompatibility in the social interaction between them, and hyperactivity demonstrated by increased locomotion in open field tests, increased grooming, and aggression episodes. Furthermore, decreases in dopamine levels and tyrosine hydroxylase activity have also been observed in flies' heads, possibly related to oxidative damage. Through analyzes of oxidative stress biomarkers, carried out on samples of flies' heads, we observed an increase in malondialdehyde and reactive species, decrease in the activity of the superoxide dismutase and catalase, which possibly culminated in the reduction of cell viability. Thus, it is important to emphasize that BPA developed atypical behaviors in Drosophila melanogaster, reinforce the importance of the environmental factor in the development of neurobehavioral diseases.
Assuntos
Comportamento Animal/efeitos dos fármacos , Compostos Benzidrílicos/toxicidade , Dopamina/metabolismo , Drosophila melanogaster/efeitos dos fármacos , Fenóis/toxicidade , Animais , Catalase/metabolismo , Dopamina/fisiologia , Drosophila melanogaster/embriologia , Drosophila melanogaster/crescimento & desenvolvimento , Feminino , Fertilidade/efeitos dos fármacos , Glutationa Transferase/metabolismo , Masculino , Teste de Campo Aberto/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Pupa/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Tirosina/metabolismo , Tirosina 3-Mono-Oxigenase/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
This study aimed to evaluate the effects of the addition of saturated fat and hydrogenated vegetable fat (HVF) to the diet on depressive and anxiety-like behaviors in Drosophila melanogaster. Flies were exposed to experimental diets: regular diet (RD), or HVF in the concentrations of the substitute (SHVF), HVF 10% and HVF 20%, or Lard (L) in the concentrations of the substitute (SL), L 10% and L 20%, during seven days. Our results showed that flies fed with the HVF diet presented similar behaviors to depression, anxiety, and a higher number of aggressive events. Flies exposed to L showed only depressive-like behavior. Regarding serotonin levels (5HT), there was a significant reduction in the flies exposed to SHVF, HVF 10%, HVF 20%, and L 20%. Regarding the levels of octopamine (OA), there was a significant reduction in the flies exposed to both HVF and L rich diets when compared with the RD group. Also, there was a significant negative correlation between 5HT or OA levels and behaviors of aggressiveness, negative geotaxis, immobility time, light/dark, and grooming in the flies. This study shows that D. melanogaster can serve as a valuable model for understanding psychiatric disorders and that the type of fatty acid (FA) offered in the diet can influence these disorders. This demonstrates the importance of the composition of the FAs in the neural pathways, being able to influence the signaling of neurotransmitters, such as 5HT and OA, and thus, cause behavioral changes.
Assuntos
Ácidos Graxos trans , Animais , Ansiedade , Dieta , Drosophila melanogaster , Ácidos Graxos , Ratos , Ratos WistarRESUMO
The pathogenesis of Parkinson's disease has not been fully clarified yet but its cause is known to be multifactorial. One of these factors is oxidative stress induced by exposure to environmental toxifiers. We studied the effect of Bisphenol A (BPA) at concentrations of 0.5 mM and 1 mM, the concentration of 1 mM corresponding to Lowest Observed Adverse Effect Level (LOAEL) for humans in adult Drosophila melanogaster. The BPA induced oxidative stress was established by increased levels of malondialdehyde, reactive species, and decreased activity of the antioxidant enzymes superoxide dismutase and catalase, and detoxificant enzyme glutathione-S-transferase. Associated with oxidative stress, there was a reduction of acetylcholinesterase activity and a reduction of dopamine levels, which are related to the decreased locomotion activity as observed in negative geotaxis, open field and equilibrium behaviors in group exposed to 1 mM of BPA. Oxidative stress also impaired mitochondrial and cellular metabolic activity in the head causing an increase in the mortality of flies exposed to both BPA concentrations. Therefore, BPA induced Parkinsonian-like changes in flies and it is possible that the oxidative stress is closely related to this effect, providing new insights for future studies.
Assuntos
Compostos Benzidrílicos/toxicidade , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/crescimento & desenvolvimento , Doença de Parkinson/etiologia , Fenóis/toxicidade , Animais , Catalase/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Feminino , Glutationa Transferase/metabolismo , Humanos , Masculino , Malondialdeído/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Nível de Efeito Adverso não Observado , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismoRESUMO
The etiopathogenesis of depression may involve repeated exposure to several unpredictable stressors. This study was conducted to investigate changes induced by chronic unpredictable mild stress (CUMS) and to assess behavioral and neurochemical changes that predict depressive-like behavior in Drosophila melanogaster. Male Drosophila melanogaster flies were exposed to CUMS with several stressors (cold, heat, starvation, and sleep deprivation) in an unpredictable and chronic manner for ten days. At the end of treatment, in vivo behavioral tests (open field, aggression, forced swimming, mating, light/dark box, male fertility evaluation, sucrose preference, weight evaluation) and ex vivo analyses (dopamine and serotonin levels) were performed. Using this CUMS model, we obtained results that contribute to the construction of a depressive model in Drosophila, where we reproduce some behavioral phenotypes corresponding to depressive symptoms, such as immobility in the forced swimming test, less exploration in the light/dark test, changes in mating behavior, changes in the aggressiveness test, reduced sucrose preference, and weight-loss, in addition to a significant reduction in the levels of serotonin and dopamine when compared to the control group. Fluoxetine was used in our study as a positive control to demonstrate that CUMS-induced depressive-like behaviors in flies can be reversed by antidepressants. In conclusion, male Drosophila melanogaster exposed to CUMS display a depressive-like phenotype, and, while this poses some limitations as an animal model for depression, it meets some of the criteria required to be a valid model, such as good face and construct validity.