Examine the local glucose dynamics in activity-induced hippocampal neurogenesis

检查活动诱导的海马神经发生中的局部葡萄糖动态

• 批准号: 10572244
• 负责人: Shaoyu Ge
• 金额: $ 43.86万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10572244
• 关键词: Activities of Daily Living; Adult; Aldolase C; Alzheimer' s Disease; Astrocytes; Behavior; Behavioral; Brain; Brain Diseases; Brain Injuries; Budgets; Cell Culture Techniques; Cell physiology; Cells; Clinical; Development; Disease; Energy Supply; Enzymes; Functional Regeneration; Generations; Glucose; Glucose Transporter; Glycolysis; Goals; Growth; Hippocampus (Brain); Individual; Learning; Measures; Mus; Nerve Regeneration; Nerve Tissue; Nervous System Trauma; Neurons; Pathologic; Physiological; Pilot Projects; Provider; Public Health; Research Proposals; Rest; Role; Seizures; Stimulus; Stroke; Structure of germinal center of lymph node; Testing; Time; Transportation; Traumatic injury; United States; adult neurogenesis; cognitive function; dentate gyrus; environmental enrichment for laboratory animals; experimental study; glucose metabolism; glucose sensor; imaging modality; improved; insight; knock-down; migration; nerve stem cell; neural circuit; neurogenesis; newborn neuron; novel therapeutics; optical imaging; relating to nervous system; repaired; response; stem cell biology; synaptogenesis

Abstract The overall goal of this proposal is to explore the local cellular glucose dynamics in regulating activity- induced hippocampal neurogenesis. Hippocampal neurogenesis sensitively responds to physiological, behavioral, and unfortunately also pathological stimuli. It has been and is continuously being an essential question: how brain activities, no matter they are physiological or pathological stimuli, regulate the generation and circuit integration of new hippocampal neurons in the adult brain. In this explorative proposal, how adult brain actively regulates the local glucose dynamics in response to brain stimuli and eventually regulates neurogenesis will be studied. Two sets of experiments have been proposed. 1) Examine the local glucose dynamics during the hippocampus-engaged behaviors. The glucose dynamics in the astroglia of the dentate gyrus during the contextual exploration will be determined. The level of glucose in astroglia will be measured in real time manner during the regular and enhanced exploration behavior. The intercellular transportation machinery of glucose-derived metabolite, lactate, in the dentate gyrus will be examined. 2) Determine the role of local glucose dynamics in regulating activity-induced hippocampal neurogenesis. The potential effect of glucose dynamics in the dentate gyrus on the survival of new hippocampal neurons will be tested. The glucose transporters of astroglial cells or neural progenitors will be knocked down and the survival of newly generated neurons will be tested. The findings will ultimately provide insights into the understanding of how the cellular glucose dynamics change in response to hippocampus-engaged behaviors and how the glucose dynamics account for the activity-induced hippocampal neurogenesis.

抽象的 该提案的总体目标是探索调节活性的局部细胞葡萄糖动力学 - 诱导海马神经发生。海马神经发生敏感地响应生理学， 行为，不幸的是病理性刺激。过去已经并且一直是必不可少的 问题：无论是生理或病理刺激，大脑活动如何调节 成人大脑中新的海马神经元的电路整合。在这个探索性建议中，如何成人 大脑积极调节局部葡萄糖动力学，以响应脑刺激，并最终调节 将研究神经发生。已经提出了两组实验。 1）检查局部葡萄糖 海马参与行为期间的动态。齿状星形胶质细胞中的葡萄糖动力学 将确定上下文探索期间的回旋。将测量星形胶质细胞中的葡萄糖水平 在常规和增强的勘探行为中实时实时。细胞间运输 将检查齿状回的葡萄糖衍生的代谢产物，乳酸的机械。 2）确定角色 调节活性诱导的海马神经发生的局部葡萄糖动力学。潜在影响 将测试齿状回生存的齿状回生存中的葡萄糖动力学。葡萄糖 星形胶质细胞或神经祖细胞的转运蛋白将被击倒，新产生的生存 神经元将进行测试。这些发现最终将提供有关对细胞如何理解的见解 葡萄糖动力学对海马引进的行为以及葡萄糖动力学的响应发生变化 考虑了活动引起的海马神经发生。