Group II metabotropic glutamate receptors in the aging brain

衰老大脑中的 II 类代谢型谷氨酸受体

• 批准号: 9353277
• 负责人: CHARLES C LEE
• 金额: $ 7.4万
• 依托单位: LOUISIANA STATE UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9353277
• 关键词: Age; Age of Onset; Age-Months; Aging; Anatomy; Animal Testing; Animals; Attention; Auditory; Auditory Brainstem Responses; Auditory area; Auditory system; Beavers; Behavior; Biological Assay; Biological Models; Brain; Brain region; Cells; Cognitive deficits; Data; Deterioration; Disease; Equilibrium; Etiology; Foundations; Future; Glutamates; Goals; Health; Hearing; Immunohistochemistry; Impairment; In Vitro; Investigation; Knowledge; Lasers; Link; Mediating; Metabotropic Glutamate Receptors; Methods; Mission; Molecular; Mouse Strains; Neocortex; Neurons; Outcome; Pathologic; Pathway interactions; Pattern; Perception; Pharmacology; Physiological; Pilot Projects; Preparation; Productivity; Prosencephalon; Public Health; Quality of life; Receptor Activation; Research; Role; Scanning; Sensory; Slice; Societies; Synapses; Testing; Time; United States National Institutes of Health; Visual; Visual Cortex; age related; aging brain; base; experience; experimental study; hearing impairment; improved; in vivo; innovation; interest; mouse model; nervous system disorder; neural circuit; neurophysiology; novel; patch clamp; prevent; prospective; receptor; receptor expression; relating to nervous system; response; therapeutic target

ABSTRACT The deterioration of neural circuits in the brain is a contributing factor to the perceptual deficits associated with aging. The long-term goals of our research are to understand the molecular and neural alterations that underlie age-related perceptual impairments. The primary objective of this R03 pilot proposal is to characterize the molecular neuropharmacological alterations to Group II metabotropic glutamate receptors (mGluRs), which enable glutamatergic inhibition at forebrain synapses. The central hypothesis is that the expression of these Group II mGluRs is altered with age in the neocortex. This is rationalized to result in changes to the balance of excitation and inhibition in the neocortex and contribute to the emergence of age-related sensory perceptual deficits. Several neuroanatomical and neurophysiological features of these receptors have been identified, which forms the basis for the proposed investigation. The specific aims of this project are to characterize the alterations to Group II mGluRs in the neocortex with age by examining: 1) changes in the neuroanatomical expression patterns of these receptors and 2) alterations to forebrain neurophysiological responses mediated by pharmacological activation of these receptors. The proposed experiments are expected to identify the age- related changes to Group II mGluRs in the neocortex and guide our future investigations aimed at directly linking these receptor alterations with the perceptual deficits experienced during aging and ultimately restoring normal behavior in this model system. These experiments will have a positive impact by illuminating the potentially important role of Group II mGluRs in age-related perceptual deficits and as a prospective therapeutic target for these conditions.

摘要 大脑中神经回路的退化是导致知觉缺陷的一个因素 衰老。我们研究的长期目标是了解分子和神经的变化 这是与年龄相关的知觉障碍的基础。此R03试点提案的主要目标是 第二类代谢性谷氨酸受体(MGluRs)的分子神经药理学变化 在前脑突触启用谷氨酸能抑制。中心假设是这些基因的表达 II组新皮质mGluRs随年龄增长而改变。这是合理的，以导致对 新皮质的兴奋和抑制，并有助于与年龄相关的感觉知觉的出现 赤字。已经确定了这些受体的几个神经解剖学和神经生理学特征， 这构成了拟议调查的基础。这个项目的具体目标是描述 新皮质中II组mGluRs随年龄的变化：1)神经解剖学的变化 这些受体的表达模式和2)前脑神经生理反应的变化 通过药物激活这些受体。拟议中的实验预计将确定年龄- 大脑皮层中第二组mGluRs的相关变化，并指导我们未来的研究，旨在直接 将这些受体的改变与衰老和最终恢复过程中经历的知觉缺陷联系起来 此模型系统中的正常行为。这些实验将产生积极的影响，通过照亮 第二组mGluRs在年龄相关性知觉缺陷中的潜在重要作用 这些疾病的治疗靶点。