Understanding the Mechanism Involved in Immune-mediated Cognitive Functioning

描述(申请人提供)：拟议研究的长期目标是研究免疫系统分子趋化因子CXCL12在认知功能中的作用。认知是一种活跃的智力过程，通过它，信息被获取、转化、存储，并被用来帮助将我们定义为个体。生存依赖于学习和记忆的健康认知功能，允许适应个人经历并促进幸福感。了解调节学习和记忆的机制将有助于优化策略的发展，以抵消认知能力的下降或丧失。越来越多的证据表明，参与损伤和炎症反应的免疫系统分子，如细胞因子，在中枢神经系统的生理发育和调节中发挥作用。目前的报告表明，细胞因子在认知功能中发挥作用，由于趋化因子与细胞因子相似，因此有理由认为它们也可能对认知产生影响。我们的初步数据表明，在正常生理条件下，特定的趋化因子CXCL12在学习和记忆中发挥作用。然而，CXCL12及其相应的受体CXCR4如何影响复杂的中枢神经系统认知功能的潜在机制尚不清楚。一种可能但知之甚少的调节学习和记忆的生理机制是成人神经发生，这是一个终生产生新神经元的过程，必须成功地整合到现有的神经元网络中，并可能代表新的记忆。调控成体神经发生的复杂过程涉及许多分子机制。我们假设，CXCL12/CXCR4信号对认知功能的影响可能是由海马区(参与学习和记忆的脑区)的内源性成人神经发生介导的，因为神经发生在学习和记忆中发挥着重要作用。因此，本研究的具体目的是研究CXCL12/CXCR4信号在神经发生中的作用及其与学习和记忆的关系。 公共卫生相关性：生存取决于学习和记忆的健康认知功能，允许适应个人经历并促进福祉。了解调节学习和记忆的细胞和分子机制将有助于优化策略的发展，以抵消认知能力的下降或丧失。

DESCRIPTION (provided by applicant): The long-term objective of the proposed study is to examine the role of the chemokine CXCL12, an immune system molecule, in cognitive functioning. Cognition is the active intellectual processes through which information is obtained, transformed, stored, and used to help define us as individuals. Survival depends upon the healthy cognitive functioning of learning and memory, allowing adaptation to individual experiences and promoting well-being. Understanding the mechanisms that regulate learning and memory will help optimize the development of strategies to offset cognitive decline or loss. Increasing evidence shows that immune system molecules involved in injury and the inflammatory response, such as cytokines, play a role in the physiologic development and modulation of the central nervous system. Current reports show that cytokines play a role in cognitive functioning and because chemokines are similar to cytokines, it is reasonable to suggest that they may also have an effect on cognition. Our preliminary data show that the specific chemokine, CXCL12, plays a role in learning and memory under normal physiological conditions. However, the underlying mechanism on how CXCL12 and its corresponding receptor, CXCR4, affect the complex central nervous system function of cognition is not well understood. A likely but poorly understood physiologic mechanism regulating learning and memory is adult neurogenesis, a life-long process of generating new neurons which must successfully integrate into an existing neuronal network and may represent new memories. The intricate process of regulating adult neurogenesis involves many molecular mechanisms. We hypothesize that effects of CXCL12/CXCR4 signaling on cognitive functioning may be mediated by endogenous adult neurogenesis in the hippocampus (brain region involved in learning and memory) given that neurogenesis has been shown to play an important role in learning and memory. Thus, the specific aim of the study is to examine the effects of CXCL12/CXCR4 signaling on neurogenesis and its relationship to learning and memory. PUBLIC HEALTH RELEVANCE: Survival depends upon the healthy cognitive functioning of learning and memory, allowing adaptation to individual experiences and promoting well-being. Understanding the cellular and molecular mechanisms that regulate learning and memory will help optimize the development of strategies to offset cognitive decline or loss.