REGULATION OF HIPPOCAMPAL DYNORPHIN LEVELS AND SYNTHESIS AFTER ISCHEMIA

缺血后海马强啡肽水平和合成的调节

• 批准号: 3945316
• 负责人: T S NOWAK
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3945316
• 关键词: brain metabolism; cerebral ischemia /hypoxia; hippocampus; messenger RNA; neurochemistry; neurotransmitter biosynthesis; neurotransmitter metabolism

Peptides derived from each of the endogenous opioid precursors were measured in gerbil brain regions after transient ischemia. Lasting depletion of dynorphin A immunoreactivity were observed only in hippocampus. Levels of hippocampal dynorphin fell by 30- 40% as early as 1 hr after recirculation and remained at 50% of control for at least one week. In some experiments peptide levels showed a transient recovery at 24 hr. Preliminary results suggest a similar reduction in hippocampal pro-dynorphin mRNA levels with a similar time course. These results demonstrate at the neurochemical level a unique sensititivity of the dynorphin-containing dentate granule cell/mossy fiber pathway to transient ischemia. Although these cells remain histologically intact, the decrease in dynorphin precedes and continues during the delayed loss of hippocampal CA1 neurons characteristic of this model and further defines the selective vulnerability of hippocampal circuitry following ischemia. The mechanisms responsible for peptide depletion, and the functional roles of dynorphin peptides in the physiology and pathology of the hippocampus, remain to be elucidated.

衍生自每种内源性阿片样物质前体的肽 在短暂缺血后在沙鼠脑区域中测量。 观察到强啡肽A免疫反应性持续耗竭 只在海马区。 海马强啡肽水平下降了30- 早在再循环后1小时即达到40%，并保持在50% 控制至少一周。 在一些实验中，肽水平 显示在24小时短暂恢复。初步结果表明， 海马强啡肽原mRNA水平也有类似的降低， 时间进程相似。 这些结果表明，在神经化学水平上， 含强啡肽齿状颗粒的敏感性 细胞/苔藓纤维通路至短暂性缺血。 虽然这些 细胞保持组织学完整，强啡肽的减少 在海马神经元延迟性丢失期间， CA 1神经元的特征，并进一步定义了 海马回路的选择性易损性 缺血 负责肽消耗的机制，以及 强啡肽在生理学中的功能作用， 海马体的病理学仍有待阐明。