Regulation of long distance neuropeptide signaling in aging

分泌囊泡的发生、运输和融合在细胞和生物体的稳态中起着重要作用。由于神经元的高度极化结构和长轴突投射，其囊泡运输面临着特殊的挑战。神经囊泡货物的运输和释放受损，如经典的神经递质、神经肽和神经营养因子，有助于与年龄相关的大脑疾病。在这个项目中，我将研究进化保守胞外机制的核心组成部分对不同类型神经元在不同成熟阶段轴突运输和分泌颗粒释放的贡献。更具体地说，我将结合使用遗传、电生理和成像工具来检查来自不同脑区（下丘脑、海马、皮层）和小鼠脑切片的小鼠初级神经元中神经肽Y （NPY）和脑源性神经营养因子（BDNF）的运输和释放。本研究结果将促进我们对老年性中枢神经系统疾病的认识。

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.