The Role of Glutamate in the Control of Food Intake

谷氨酸在控制食物摄入量中的作用

• 批准号: 7177705
• 负责人: Robert C Ritter
• 金额: $ 26.19万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7177705
• 关键词: AMPA Receptors; Ablation; Accounting; Acids; Acute; Afferent Neurons; Agonist; Appetitive Behavior; Area; Behavioral; Body Weight; Brain; Calories; Categories; Chemical Stimulation; Chemicals; Cholinergic Receptors; Chronic; Computer Assisted; Consumption; Data; Development; Dicarboxylic Amino Acids; Dorsal; Eating; Emotional; Excitatory Amino Acid Antagonists; Feedback; Feeding behaviors; Fiber; Food; GTP-Binding Proteins; Gastric Emptying; Gastrointestinal tract structure; Gated Ion Channel; Glutamate Receptor; Glutamates; Hand; Hour; Hypothalamic structure; Intake; Intestines; Ion Channel; Isoxazoles; Kynurenic Acid; Lateral; Lesion; Ligands; Link; Measures; Mechanical Stimulation; Microinjections; Midbrain structure; Monitor; Morbidity - disease rate; Motor; Motor Activity; Muscarinics; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Nervous system structure; Neurons; Neurotransmitter Receptor; Neurotransmitters; Nucleus solitarius; Obesity; Peripheral; Physiological; Progress Reports; Propionic Acids; Propionic acid; Prosencephalon; Rate; Rattus; Reporting; Role; Satiation; Second Messenger Systems; Sensory; Signal Transduction; Societies; Stimulus; Stomach; Substance P; Techniques; Water consumption; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; amino 3 hydroxy 5 methylisoxazole 4 propionate; deprivation; drinking; falls; feeding; hindbrain; improved; kainate; mortality; neurochemistry; neuroregulation; quisqualate; receptor; relating to nervous system; response; size; social

Obesity accounts for significant morbidity and mortality in the USA, as well as Western societies in general. The development of obesity can often be linked to a consumption of excess calories. Clearly, people eat in response to a variety of stimuli--physiological, environmental, emotional and social. However, improving our understanding of the neural controls of food intake may provide concrete measures by which obesity can be avoided. Meal termination usually begins with the propagation of sensory signals from the gut. For example, both mechanical stimulation of the stomach, and chemical stimulation of the intestine provide negative feedback that contributes to termination of food intake (satiation). Although vagal sensory neurons are known to convey both gastric mechanosensitive and intestinal chemosensitive signals to the brain, little is known about the neurotransmitters and receptors that communicate these signals from the vagus, to and through the brain. Several years ago, we have demonstrated that ionotropic; N-methyl-D-aspartate receptors (NMDA receptors) participate in termination of food intake. Our more recent results indicate that NMDA receptors specifically participate in satiety by altering gastric motor activity. In support of this hypothesis, we have compiled evidence to suggest that NMDA receptors involved in termination of feeding are located in the dorsal hindbrain, where vagal motor fibers from the gastrointestinal tract arise. These motor fibers act to control food intake via muscarinic cholinergic receptors to modulate the rate of gastric emptying. Furthermore, preliminary data from our lab suggest that substance P neurons and/or neurotachyldnin receptors may be important neural substrates for this effect. Accordingly, the specific aims that we have outlined for this renewal application are: 1) to employ physical/chemical ablation to reveal the central and peripheral neural and neurochemical substrates that contribute to increases in meal size induced by systemic MK-801; 2) to utilize a combination of behavioral and physiological techniques to determine the qualitative and quantitative relationships between altered within-meal gastric motor functions and increased food intake evoked by MK-801; and, 3) to make use of computer-assisted monitoring and analysis of meal parameters, in combination with acute and chronic administration of NMDA receptor antagonists, to determine the role of NMDA receptors in control of spontaneous meal size, 24-hour food intake, and body weight.

在美国以及整个西方社会，肥胖是造成显着发病率和死亡率的原因。 肥胖的发生通常与摄入过多热量有关。显然，人们在吃饭时 对各种刺激的反应——生理的、环境的、情感的和社会的。然而，改善 我们对食物摄入的神经控制的理解可能会提供具体的措施，通过这些措施肥胖可以 应避免。进餐终止通常始于肠道感觉信号的传播。为了 例如，胃的机械刺激和肠道的化学刺激都提供 导致食物摄入终止（饱腹感）的负反馈。虽然迷走神经感觉神经元 已知可以向大脑传递胃机械敏感信号和肠道化学敏感信号，但很少有人知道 了解将这些信号从迷走神经传递到和的神经递质和受体 通过大脑。几年前，我们已经证明了离子变性； N-甲基-D-天冬氨酸受体 （NMDA 受体）参与食物摄入的终止。我们最近的结果表明 NMDA 受体通过改变胃运动活动专门参与饱腹感。为了支持这个假设，我们 已收集的证据表明，参与终止进食的 NMDA 受体位于 背侧后脑，来自胃肠道的迷走神经运动纤维在此产生。这些运动纤维的作用是 通过毒蕈碱胆碱能受体控制食物摄入，调节胃排空速率。 此外，我们实验室的初步数据表明 P 物质神经元和/或神经速胺 受体可能是这种效应的重要神经基质。因此，我们的具体目标 该更新应用概述为：1）采用物理/化学消融来揭示中央和 外周神经和神经化学底物有助于全身性引起的膳食量增加 MK-801； 2）结合行为和生理技术来确定定性 餐内胃运动功能改变与食物摄入量增加之间的定量关系 由 MK-801 诱发； 3) 利用计算机辅助监测和分析膳食参数， 结合急性和慢性施用 NMDA 受体拮抗剂，以确定其作用 NMDA 受体控制自发进餐量、24 小时食物摄入量和体重。