The modulation of adenosine by temperature, oxygen and glucose

温度、氧气和葡萄糖对腺苷的调节

• 批准号: 7669851
• 负责人: SUSAN A MASINO
• 金额: $ 3.8万
• 依托单位: TRINITY COLLEGE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-15 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7669851
• 关键词: Acute; Adenosine; Adenosine A1 Receptor; Adenosine Triphosphate; Basic Science; Biochemistry; Biological Models; Brain; Brain Hypoxia-Ischemia; Brain region; Charge; Clinical; Condition; Disease; Electrophysiology (science); Energy Supply; Epilepsy; Genetic; Genotype; Glucose; Heterozygote; Hippocampus (Brain); Hypoglycemia; Laboratories; Laboratory Research; Link; Mus; Nervous system structure; Neurons; Neurosciences; Numbers; Oxygen; Pain; Parkinson Disease; Pathology; Pharmacology; Physiological; Physiology; Play; Purinergic P1 Receptors; Range; Rate; Rattus; Recovery; Regulation; Relative (related person); Research; Role; Scientist; Sleep Disorders; Slice; Spinal cord injury; Stroke; Synaptic Transmission; Temperature; Therapeutic; Thinking; Time; Training; Wild Type Mouse; clinically significant; deprivation; fundamental research; interest; mutant; receptor; research study; synaptic inhibition; therapeutic target

DESCRIPTION (provided by applicant): Adenosine is found throughout the nervous system, and its interaction with specific adenosine receptors modulates ongoing neuronal activity in many brain regions. As the core molecule of adenosine triphosphate (ATP), and a component of the overall cellular energy charge, adenosine provides a unique cellular link between energy demand and brain function. The specific inhibitory influence of the adenosine A1 receptor subtype reduces activity and helps neurons survive a short-term compromised energy supply, such as during insufficient oxygen or glucose. Its modulation of physiology and protection against pathology make adenosine a coveted therapeutic target for disorders as diverse as pain, Parkinson's disease, stroke, epilepsy, and sleep disorders. Accumulated research shows that adenosine levels are altered significantly by changes in temperature, pH, oxygen and glucose. The objective of this proposal is to elucidate the relationship between adenosine and these physiologically-relevant variables to inform and benefit both basic research and clinical conditions. The specific aims outlined herein quantify the influence of adenosine across the typical range of recording temperatures in the hippocampal slice, and systematically examine the effect(s) of reducing available oxygen and/or glucose using a combination of electrophysiology, pharmacology and genetically modified mice. Beyond the clinical significance, the proposed studies are relevant to understanding features of the model systems we use in neuroscience, and they represent a succinct set of fundamental research experiments useful as a training platform for young scientists. Ultimately, understanding the regulation of endogenous adenosine, its influence on widely used model systems, and its functional consequences during pathological conditions will enable us to explore and enhance its therapeutic possibilities in situations as diverse as stroke, epilepsy and spinal cord injury.

描述（由申请人提供）：在整个神经系统中发现腺苷，其与特异性腺苷受体的相互作用调节许多脑区域中正在进行的神经元活动。作为三磷酸腺苷（ATP）的核心分子和整体细胞能量电荷的组成部分，腺苷在能量需求和大脑功能之间提供了独特的细胞联系。腺苷A1受体亚型的特异性抑制作用降低了活性，并帮助神经元在短期受损的能量供应中存活下来，例如在氧气或葡萄糖不足的情况下。腺苷对生理的调节和对病理的保护使其成为疼痛、帕金森病、中风、癫痫和睡眠障碍等多种疾病的令人垂涎的治疗靶点。累积的研究表明，腺苷水平会因温度、pH值、氧气和葡萄糖的变化而显著改变。本提案的目的是阐明腺苷与这些生理相关变量之间的关系，以告知基础研究和临床条件并使其受益。本文概述的具体目的是量化腺苷在海马切片中记录温度的典型范围内的影响，并使用电生理学、药理学和遗传修饰小鼠的组合系统地检查减少可用氧和/或葡萄糖的作用。除了临床意义之外，拟议的研究与理解我们在神经科学中使用的模型系统的特征有关，它们代表了一组简洁的基础研究实验，可作为年轻科学家的培训平台。最终，了解内源性腺苷的调节，其对广泛使用的模型系统的影响，以及其在病理条件下的功能后果，将使我们能够探索和提高其在中风，癫痫和脊髓损伤等不同情况下的治疗可能性。

项目成果

Metabolic autocrine regulation of neurons involves cooperation among pannexin hemichannels, adenosine receptors, and KATP channels.

• DOI: 10.1523/jneurosci.0055-10.2010
• 发表时间: 2010-03-17
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Kawamura M Jr;Ruskin DN;Masino SA
• 通讯作者: Masino SA

Reduced pain and inflammation in juvenile and adult rats fed a ketogenic diet.

• DOI: 10.1371/journal.pone.0008349
• 发表时间: 2009-12-23
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Ruskin DN;Kawamura M;Masino SA
• 通讯作者: Masino SA