CATECHOLAMINES IN AGING AND OXIDATIVE STRESS

氧化应激和炎症已被认为在衰老和衰老过程中起关键作用。 与衰老相关的神经退行性疾病，如阿尔茨海默病和帕金森病。 因此，了解大脑中导致炎症增加的机制， 氧化应激可能导致衰老和神经变性疾病的合理治疗干预。 我们一直在研究营养干预措施，如菠菜或蓝莓，这会导致 改善老年大鼠的学习和记忆，以及调节许多脑老化的生物标志物。在 在过去的授权期间，我们已经证明，炎症和氧化应激发生在老年人 这些过程可能导致认知功能的下降。我们有 证明了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，这是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。一个潜在 其机制是改善炎症随年龄的增加。小胶质细胞是一种重要的 脑中活性氧（ROS）的来源以及其他炎症信号，如促炎信号， 细胞因子，因此可能在调节CNS氧化应激和 神经退行性疾病我们计划研究免疫功能的进展， 老年脑神经变性和神经变性治疗干预的潜力 老年痴呆症等疾病。我们假设氧化应激和炎症是 老年大脑中神经元功能障碍的主要驱动因素;此外，小胶质细胞中与年龄相关的变化 是大脑老化和神经退行性疾病的关键主要事件。具体到 小脑，小胶质细胞产生肿瘤坏死因子（TNF）α导致进一步的炎症， 氧化应激减少TNF α和/或小胶质细胞活化的治疗干预将 在老年动物中改善神经元功能以及伴随学习和记忆将 提高

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.