Interleukin-1 and Memory Loss in Aging

Interleukin-1 与衰老导致的记忆丧失

• 批准号: 7084460
• 负责人: CARMELINA GEMMA
• 金额: $ 20.32万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7084460
• 关键词: aging; animal old age; apoptosis; behavioral /social science research tag; cysteine endopeptidases; enzyme activity; hippocampus; inflammation; interleukin 1; laboratory rat; memory disorders; neural plasticity; neuroprotectants; protease inhibitor

DESCRIPTION (provided by applicant): The primary hypothesis of this grant is that chronic inflammation and apoptosis lead to hippocampusdependent behavioral deficits. There is accumulating evidence for the role of IL1b in learning and memory. In aged rats there is an increase in IL1b that has been implicated in declines of synaptic plasticity in the hippocampus and performance on cognitive tasks. There are several questions about the role of this cytokine in learning and memory processes that remain unanswered. 1) Are increased levels of IL-1 directly responsible for deficits in learning and memory occurring in normal age? 2) Is IL-1 presence at physiological levels in young rats a limiting-step in the acquisition and storage of memory? 3) and finally, which are the mechanisms by which IL-1 affects memory? Many elderly individuals exhibit deficits in learning and memory processes, as well as decreased numbers of neurons in different regions of the brain. However, the development of more accurate procedures for counting neurons, such as the use of stereology, has raised doubts about the decline in neurons number, via neuronal death during normal aging. If significant neuronal loss is lacking, several pathological features of neurodegeneration, such as the presence of Lewy bodies, typical of Parkinson's disease, and senile plaques, typical of Alzheimer's disease, can be detected in brains of aged individuals. So, the question that has been raised from these observations is whether or not apoptosis, beyond its involvement in neuronal death, affects the decline in cognitive processes occurring during normal aging. Caspases are a family of proteases that play a critical role in long-term spatial memory storage. Caspase-1 (IL-1b converting enzyme) has the peculiarity of being involved in the activation of both apoptosis and inflammation, through the intermediate of IL-1b. It has been shown that inhibition of caspase-1 induces neuroprotection in cerebral ischemia through apoptosis reduction and decrease of proirrflammatory cytokines. Although interleukin-1b is highly expressed in neurodegenerative disease, is involved in cognitive impairment, and induces cell death in glial cells cultures, whether IL-1b and caspase interact each other to express their effects on learning and memory, it is still unknown.

描述（由申请人提供）： 该资助的主要假设是慢性炎症和细胞凋亡导致海马依赖性行为缺陷。越来越多的证据表明 IL1b 在学习和记忆中的作用。在老年大鼠中，IL1b 增加，这与海马突触可塑性和认知任务表现的下降有关。关于这种细胞因子在学习和记忆过程中的作用，还有几个问题尚未得到解答。 1) IL-1 水平升高是否直接导致正常年龄的学习和记忆缺陷？ 2) 幼鼠生理水平上的 IL-1 是否是记忆获取和存储的限制步骤？ 3) 最后，IL-1 影响记忆的机制是什么？许多老年人表现出学习和记忆过程的缺陷，以及大脑不同区域神经元数量的减少。然而，更准确的神经元计数程序的发展，例如体视学的使用，引起了人们对正常衰老过程中神经元死亡导致的神经元数量下降的怀疑。如果缺乏显着的神经元损失，则可以在老年人的大脑中检测到神经变性的几种病理特征，例如帕金森病的典型路易体和阿尔茨海默病的典型老年斑的存在。因此，从这些观察中提出的问题是，细胞凋亡除了参与神经元死亡之外，是否还会影响正常衰老过程中发生的认知过程的衰退。 Caspases 是一个蛋白酶家族，在长期空间记忆存储中发挥着关键作用。 Caspase-1（IL-1b 转换酶）具有通过 IL-1b 中间体参与细胞凋亡和炎症激活的特性。研究表明，抑制 caspase-1 可通过减少细胞凋亡和促炎细胞因子的减少来诱导脑缺血中的神经保护。尽管IL-1b在神经退行性疾病中高表达，参与认知障碍，并在神经胶质细胞培养物中诱导细胞死亡，但IL-1b和Caspase是否相互作用以表达对学习和记忆的影响，目前仍不清楚。