CATECHOLAMINES IN AGING AND OXIDATIVE STRESS

儿茶酚胺在衰老和氧化应激中的作用

• 批准号: 7092790
• 负责人: PAULA C BICKFORD
• 金额: $ 19.35万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7092790
• 关键词: Alzheimer' s disease; Cyanophyta; aging; angiosperms; antioxidants; association learning; bacterial proteins; catecholamines; cerebellum; diet therapy; dietary supplements; fruit; genetically modified animals; laboratory mouse; mitochondria; neurogenetics; neuropharmacology; neuroprotectants; nonhuman therapy evaluation; nutrition related tag; oxidative stress; premature aging; tumor necrosis factor alpha; vegetables

Oxidative stress and inflammation have been proposed to play key roles in aging and neurodegenerative diseases associated with aging such Alzheimer's disease and Parkinson's disease. Thus, an understanding of the mechanisms in the brain that leads to an increase in inflammation and oxidative stress could lead to rational therapeutic interventions in aging and neurodegenerative diseases. We have been examining nutritional interventions such as spinach or blueberries, which lead to improvements in learning and memory in aged rats and modulation of many biomarkers of brain aging. In the past granting period, we have demonstrated that inflammation and oxidative stress occur in the aged brain and that these processes may contribute to the declines in cognitive function. We have demonstrated that both natural and pharmaceutical antioxidant and anti-inflammatory agents are capable of improving cognitive deficits in aged rats and this is concomitant with changes in neuronal signal transduction. We will examine potential mechanisms by which these diets alter brain aging. One potential mechanism is an amelioration of an increase in inflammation with age. Microglial cells are an important source of reactive oxygen species (ROS) in the brain as well as other inflammatory signals such as proinflammatory cytokines and therefore may play a central role in modulating CNS oxidative stress and neurodegenerative diseases. We plan to investigate immune function in the progression of neurodegeneration in the aged brain and the potential for therapeutic intervention in neurodegenerative diseases such as Alzheimer's disease. We hypothesize that oxidative stress and inflammation are primary drivers of neuronal dysfunction in the aged brain; furthermore, age-related changes in microglia are the critical primary events in brain aging and neurodegenerative disease. Specifically, in the cerebellum, microglial production of tumor necrosis factor (TNF)alpha leads to further inflammation and oxidative stress. Therapeutic interventions that reduce TNFalpha and/or microglial activation will improve neuronal function and concomitantly learning and memory in aged animals will be improved.

氧化应激和炎症已被认为在衰老和衰老过程中发挥着关键作用。 与衰老相关的神经退行性疾病，例如阿尔茨海默病和帕金森病。 因此，了解大脑中导致炎症和炎症增加的机制 氧化应激可能导致对衰老和神经退行性疾病的合理治疗干预。 我们一直在研究菠菜或蓝莓等营养干预措施，这会导致 改善老年大鼠的学习和记忆以及调节大脑衰老的许多生物标志物。在 在过去的资助期间，我们已经证明炎症和氧化应激发生在老年人中 大脑，这些过程可能会导致认知功能下降。我们有 证明天然和药物抗氧化剂和抗炎剂都能够 改善老年大鼠的认知缺陷，这伴随着神经元信号的变化 转导。我们将研究这些饮食改变大脑衰老的潜在机制。一种潜力 机制是改善随着年龄增长而增加的炎症。小胶质细胞是一个重要的细胞 大脑中活性氧 (ROS) 以及其他炎症信号（如促炎症）的来源 细胞因子，因此可能在调节中枢神经系统氧化应激和 神经退行性疾病。我们计划研究疾病进展过程中的免疫功能 老年大脑的神经退行性疾病以及神经退行性疾病治疗干预的潜力 阿尔茨海默病等疾病。我们假设氧化应激和炎症是 老年大脑神经元功能障碍的主要驱动因素；此外，小胶质细胞的年龄相关变化 是大脑衰老和神经退行性疾病的关键主要事件。具体来说，在 小脑中，小胶质细胞产生肿瘤坏死因子（TNF）α，导致进一步的炎症和 氧化应激。减少 TNFα 和/或小胶质细胞活化的治疗干预措施将 改善神经元功能，同时提高老年动物的学习和记忆能力 改善了。