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.

摘要 这项建议的总体目标是探索局部细胞葡萄糖动力学在调节活动- 诱导海马神经发生。海马神经发生对生理性的、 行为的，不幸的也是病理性的刺激。它一直是，并将继续是一个必不可少的 问：无论是生理的还是病理的刺激，大脑活动是如何调节生成的？ 以及成年大脑中新的海马神经元的电路整合。在这个探索性的提案中，有多成熟 大脑主动调节局部葡萄糖动态以响应大脑刺激，并最终调节 将对神经发生进行研究。已经提出了两组实验。1)检测局部血糖 海马区参与行为的动态变化。海马齿状星形胶质细胞的葡萄糖动态变化 在上下文探索期间的脑回将被确定。将测量星形胶质细胞中的葡萄糖水平 在勘探期间以实时的方式进行常规和增强的勘探行为。细胞间运输 我们将研究葡萄糖代谢产物乳酸在齿状回中的作用机制。2)确定角色 局部葡萄糖动力学在调节活动诱导的海马神经发生中的作用。潜在的影响 葡萄糖在海马齿状回的动态变化对新生海马神经元的存活率将进行测试。葡萄糖 星形胶质细胞或神经前体细胞的转运体将被击倒，新生的 神经元将接受测试。这些发现最终将为理解细胞如何 葡萄糖动力学对海马区行为的响应变化以及葡萄糖动力学如何 说明了活动诱导的海马神经发生。