ABSTRACT
Brain-derived neurotrophic factor (BDNF) induces activation of the TrkB receptor and several downstream pathways (MAPK, PI3K, PLC-γ), leading to neuronal survival, growth, and plasticity. It has been well established that TrkB signaling regulation is required for neurite formation and dendritic arborization, but the specific mechanism is not fully understood. The non-receptor tyrosine kinase c-Abl is a possible candidate regulator of this process, as it has been implicated in tyrosine kinase receptors' signaling and trafficking, as well as regulation of neuronal morphogenesis. To assess the role of c-Abl in BDNF-induced dendritic arborization, wild-type and c-Abl-KO neurons were stimulated with BDNF, and diverse strategies were employed to probe the function of c-Abl, including the use of pharmacological inhibitors, an allosteric c-Abl activator, and shRNA to downregulates c-Abl expression. Surprisingly, BDNF promoted c-Abl activation and interaction with TrkB receptors. Furthermore, pharmacological c-Abl inhibition and genetic ablation abolished BDNF-induced dendritic arborization and increased the availability of TrkB in the cell membrane. Interestingly, inhibition or genetic ablation of c-Abl had no effect on the classic TrkB downstream pathways. Together, our results suggest that BDNF/TrkB-dependent c-Abl activation is a novel and essential mechanism in TrkB signaling.
Subject(s)
Brain-Derived Neurotrophic Factor , Neurons , Brain-Derived Neurotrophic Factor/metabolism , Cells, Cultured , Neurons/metabolism , Receptor, trkB/genetics , Receptor, trkB/metabolism , Signal Transduction , Proto-Oncogene Proteins c-ablABSTRACT
Este estudio presenta la caracterización del insomnio en estudiantes de medicina de la Universidad Tecnológica de Pereira durante el segundo semestre del 2011. Se usó como instrumento el test de Pittsburgh, más una serie de preguntas referentes a la higiene del sueño y variables demográficas de importancia. Con los datos recolectados se realizó análisis univariado y bivariado. Resultados: 76% de la población fue clasificada como malos dormidores, 60% de los cuales está constantemente expuestos a situaciones estresantes. El 58% de la población presentó insomnio ocasional o transitorio, 11% insomnio de corta duración, 11% insomnio crónico y el 20% restante no presentó insomnio. Conclusiones: Los estudiantes del programa de medicina y cirugía de la Universidad Tecnológica de Pereira se encuentran expuestos constantemente a situaciones estresantes lo cual influye significativamente de manera negativa en su calidad del dormir manifestada en calificaciones del ICSP elevadas y el consecuente desarrollo de insomnio.
This study presents the characterization of the insomnia inmedicine students from the Universidad Tecnológica de Pereira during the second academic semester of 2011. It was implemented the sleep quality test of Pittsburgh, plusa series of questions concerning to the sleep hygiene and demographic variables of importance. With the recollected data were realized bivariate and univariate analysis. Results:76% of the studied population has been classified as badsleepers, 60% of them are constantly exposed to stressing situations. The 58% of the population presented occasional or transitory insomnia, 11% short duration insomnia, 11%chronic insomnia and the left 20% didnt presented insomnia. Conclusions: The students of the program of medicine and surgery from the Universidad Tecnológica de Pereira are constantly exposed to stressing situations which adversely influences their sleep quality as manifested in their high PSQI qualifications and the consequent development of insomnia.
