A lifespan approach to neuroinflammatory and cognitive disorders: a critical role for glia.
A lifespan approach to neuroinflammatory and cognitive disorders: a critical role for glia.
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DOI：
10.1007/s11481-011-9299-y
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发表时间：
2012-03
影响因子：
6.2
通讯作者：
Schwarz, Jaclyn M.
中科院分区：
文献类型：
--
作者：
Bilbo, Staci D.;Smith, Susan H.;Schwarz, Jaclyn M.
认知能力下降是衰老的常见问题。虽然多种神经和神经胶质机制可能导致这些下降，但小胶质细胞致敏和/或营养不良已成为脑老化和功能障碍的罪魁祸首。然而，在正常脑老化中也一致地观察到胶质细胞活化，独立于明显的神经炎症或功能障碍。这种变异性表明存在额外的脆弱性因素，这些因素可能会影响神经元-神经胶质细胞的相互作用，从而影响整体大脑和认知健康。这篇综述的目的是阐明我们的工作假设，即一个人对神经炎症性疾病和认知老化不良的风险或恢复力可能严重依赖于他们的早期生活经验，这可能会改变大脑中的免疫反应性，从而影响其寿命。例如，大鼠的早期感染可能会严重破坏年轻人的记忆功能，并加速与年龄相关的认知能力下降，这两者都与初始感染引起的神经胶质功能的持久变化有关。我们讨论这些发现的背景下，越来越多的文献中的免疫分子和神经免疫串扰的作用，在正常的大脑发育。我们强调内在因素（例如，趋化因子、激素），其调节小胶质细胞发育及其在胚胎和出生后脑中的定殖，以及外部事件（例如，压力、感染）对这一关键过程的破坏或“重新编程”的能力。对神经胶质细胞的影响，进而改变神经发育，有能力深刻影响生命各个阶段的认知和心理健康功能。
Cognitive decline is a common problem of aging. Whereas multiple neural and glial mechanisms may account for these declines, microglial sensitization and/or dystrophy has emerged as a leading culprit in brain aging and dysfunction. However, glial activation is consistently observed in normal brain aging as well, independent of frank neuroinflammation or functional impairment. Such variability suggests the existence of additional vulnerability factors that can impact neuronal-glial interactions and thus overall brain and cognitive health. The goal of this review is to elucidate our working hypothesis that an individual‘s risk or resilience to neuroinflammatory disorders and poor cognitive aging may critically depend on their early life experience, which can change immune reactivity within the brain for the remainder of the lifespan. For instance, early-life infection in rats can profoundly disrupt memory function in young adulthood, as well as accelerate age-related cognitive decline, both of which are linked to enduring changes in glial function that occur in response to the initial infection. We discuss these findings within the context of the growing literature on the role of immune molecules and neuroimmune crosstalk in normal brain development. We highlight the intrinsic factors (e.g., chemokines, hormones) that regulate microglial development and their colonization of the embryonic and postnatal brain, and the capacity for disruption or “re-programming” of this crucial process by external events (e.g, stress, infection). An impact on glia, which in turn alters neural development, has the capacity to profoundly impact cognitive and mental health function at all stages of life.
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影响因子：
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