Regulation of long distance neuropeptide signaling in aging

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Biogenesis, transport and fusion of secretory vesicles play a fundamental role in cellular and organismal homeostasis. Vesicle trafficking in neurons faces particular challenges due to their highly polarized structure and long axonal projections. Impaired trafficking and release of neuronal vesicular cargos, such as classical neurotransmitters, neuropeptides, and neurotrophic factors, contribute to age-related diseases of the brain. In this project, I will examine contribution of the core components of the evolutionary conserved exocytotic machinery to the axonal trafficking and release of secretory granules in different neuronal types at different stages of their maturation. More specifically, I will use combination of genetic, electrophysiological and imaging tools to examine trafficking and release of neuropeptide Y (NPY) and brain-derived neurotrophic factor (BDNF) in mouse primary neurons from different brain areas (hypothalamus, hippocampus, cortex) and in mouse brain slices. Results of this study will promote our understanding of the age-related diseases of the central nervous system.