The neurotransmitter for calorie

卡路里的神经递质

• 批准号: 10448263
• 负责人: Laura Eloise Rupprecht
• 金额: $ 7.44万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10448263
• 关键词: Adult; Area; Biological; Biological Assay; Biological Process; Biology; Body Weight; Brain; Calcium; Calories; Carbohydrates; Cell Culture Techniques; Cells; Complement; Data; Desire for food; Development; Development Plans; Disease; Duodenum; Eating; Electrophysiology (science); Enteroendocrine Cell; Epithelial Cells; Fatty acid glycerol esters; Fellowship; Gastroenterology; Glutamates; Goals; Growth; Hormones; Hour; Image; Individual; Intake; Intestines; Knowledge; Laboratories; Lead; Macronutrients Nutrition; Maintenance; Maps; Mentors; Motivation; Mus; Names; National Research Service Awards; Nerve; Neurobiology; Neurons; Neurotransmitters; Nodose Ganglion; Nutrient; Obesity; Optics; Organoids; Perfusion; Pharmacology; Pharmacotherapy; Population; Public Health; Research; Research Design; Research Personnel; Resolution; Science; Sensory; Signal Transduction; Small Intestines; Sucrose; Sweetening Agents; Synapses; Testing; Transgenic Mice; United States National Institutes of Health; Vagus nerve structure; Weight Gain; Work; base; calcium indicator; career development; energy density; feeding; gastrointestinal epithelium; glutamatergic signaling; gut-brain axis; in vivo; intestinal epithelium; millisecond; neural circuit; neurotransmission; novel; obesity treatment; preference; recruit; response; sugar; treatment strategy; two photon microscopy; two-photon

PROJECT SUMMARY/ABSTRACT The main motivation to feed is to obtain energy from nutrients. Thus, the maintenance of body weight depends upon circuits which recognize the value of nutrients to guide food intake. The sensory cell of the gut, the enteroendocrine cell, communicates to the brain via hormones to regulate food intake over tens of minutes to hours. In 2018, we discovered that a subset of enteroendocrine cells make synaptic contact with the vagus nerve. We named these synpatically connected cells neuropod cells. Neuropod cells communicate the presence of carbohydrate in the duodenum to the vagus nerve within 60 milliseconds using glutamate neurotransmission. However, the information encoded by glutamate is unknown. This application tests the hypothesis that glutamate neurotransmission from gut to the vagus nerve encodes the energy value of nutrients. This hypothesis will be tested in two specific aims. Specific Aim 1 will use organoid (“mini gut”) and enteroendocrine cell culture from mice to examine glutamate release in response to nutrient stimulation. We hypothesize that glutamate released from enteroendocrine cells encodes nutrient value, based upon the unit energy provided by the nutrient (i.e, kilocalorie) rather than the macronutrient content. Therefore, we predict that glutamate will be released in a kilocalorie-dependent, rather than a macronutrient-dependent manner. Specific Aim 2 will use in vivo multiphoton calcium imaging of the vagal nodose ganglia in transgenic mice which express the calcium indicator GCaMP6s in vagal nodose neurons. Single cell resolution of vagal neuron activity will be recorded in response to nutrient delivery to the duodenum. If neuropod cell glutamate release conveys information specific about energy value, rather than macronutrient content, then separate macronutrients of equal caloric value should stimulate overlapping vagal neuron populations. By defining the functional relevance for rapid gut-to-vagus glutamatergic signaling, these studies will provide new fundamental biology of gut-brain communication. This work will contribute new possible avenues of pharmacotherapies for the treatment of nutrient-intake related disease, namely obesity.

项目摘要/摘要 进食的主要动机是从营养中获取能量。那，体重的维持取决于 在确认营养物质引导食物摄入量的价值的电路上。肠道的感觉细胞， 肠内分泌细胞，通过激素传达大脑，以调节食物的摄入量，以在数十分钟内 小时。在2018年，我们发现一部分肠内分泌细胞与迷走神经接触 尼夫。我们命名了这些合成连接的细胞神经足类细胞。神经足类细胞传达 使用谷氨酸在DuodeNum中存在碳氢酸盐，直达迷走神经 神经传递。但是，谷氨酸编码的信息尚不清楚。此应用程序测试 假设从肠道到迷走神经的谷氨酸神经传递编码的能量值 营养。该假设将以两个具体的目的进行检验。特定的目标1将使用类器官（“迷你肠”）和 小鼠的肠内分泌细胞培养，以检查谷氨酸对营养刺激的释放。我们 假设从肠内分泌细胞释放的谷氨酸根据单位编码营养价值 营养素（即千瓦）而不是大量营养素含量提供的能量。因此，我们预测 该谷氨酸将以千瓦的依赖性而不是大量营养素依赖性方式释放。 特定的目标2将在转基因小鼠中使用迷走神经节的体内多光子钙成像 在迷走神经元中表达钙指示剂GCAMP6s。迷走神经元的单细胞分辨率 将记录活动，以响应对十二指肠的营养递送。 if神经脚架细胞谷氨酸释放 传达有关能量值的特定信息，而不是大量营养素含量，然后分开 相等卡路里值的大量营养素应刺激重叠的迷走神经元种群。通过定义 这些研究将提供新的基本基础 肠道交流的生物学。这项工作将为药物治疗的新途径提供 养分相关疾病的治疗，即肥胖。