RESUMEN
Insulin, a highly conserved peptide hormone, links nutrient availability to metabolism and growth in animals. In fed states insulin levels remain high and in animals that are food deprived insulin signalling drops. Here, we report that in Drosophila, feeding elicited by short periods of starvation is dependent on insulin signalling. The activity of insulin signalling pathway in the abdominal fatbody aids in feeding during short periods of starvation. A feedback regulatory signalling that involves cells that express the Drosophila hunger hormone short-neuropeptide-F (sNPF) and insulin-producing cells sustain the orexigenic function of insulin. Furthermore, the orexigenic phase of insulin activity aids in the efficient management of nutrient stores and survival of flies during starvation.
Asunto(s)
Drosophila/metabolismo , Conducta Alimentaria/fisiología , Hambre/fisiología , Insulina/metabolismo , Transducción de Señal/genética , Animales , Encéfalo/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Ingestión de Alimentos/genética , Metabolismo Energético/genética , Células Secretoras de Insulina/metabolismo , Masculino , Neuronas/metabolismo , Neuropéptidos/genética , Neuropéptidos/metabolismo , Interferencia de ARN , Inanición/genética , Inanición/metabolismoRESUMEN
Anxiety and depression are major chronic mood disorders, and the etiopathology for each appears to be repeated exposure to diverse unpredictable stress factors. Most of the studies on anxiety and related mood disorders are performed in rodents, and a good model is chronic unpredictable stress (CUS). In this study, we have attempted to understand the molecular basis of the neuroglial and behavioral changes underlying CUS-induced mood disorders in the simplest vertebrate model, the zebrafish, Danio rerio. Zebrafish were subjected to a CUS paradigm in which two different stressors were used daily for 15 days, and thorough behavioral analyses were performed to assess anxiety and related mood disorder phenotypes using the novel tank test, shoal cohesion and scototaxis. Fifteen days of exposure to chronic stressors appears to induce an anxiety and related mood disorder phenotype. Decreased neurogenesis, another hallmark of anxiety and related disorders in rodents, was also observed in this zebrafish model. The common molecular markers of rodent anxiety and related disorders, corticotropin-releasing factor (CRF), calcineurin (ppp3r1a) and phospho cyclic AMP response element binding protein (pCREB), were also replicated in the fish model. Finally, using 2DE FTMS/ITMSMS proteomics analyses, 18 proteins were found to be deregulated in zebrafish anxiety and related disorders. The most affected process was mitochondrial function, 4 of the 18 differentially regulated proteins were mitochondrial proteins: PHB2, SLC25A5, VDAC3 and IDH2, as reported in rodent and clinical samples. Thus, the zebrafish CUS model and proteomics can facilitate not only uncovering new molecular targets of anxiety and related mood disorders but also the routine screening of compounds for drug development.