Department of Psychology and Neuroscience, University of Colorado at Boulder, Boulder, CO 80309, USA.
Horm Behav. 2012 Aug;62(3):219-27. doi: 10.1016/j.yhbeh.2012.02.010. Epub 2012 Feb 18.
Healthy aged individuals are more likely to suffer profound memory impairments following a challenging life event such as a severe bacterial infection, surgery, or an intense psychological stressor, than are younger adults. Importantly, these peripheral challenges are capable of producing a neuroinflammatory response, (e.g., increased pro-inflammatory cytokines). In this review we will present the literature demonstrating that in the healthy aged brain this response is exaggerated and prolonged. Normal aging primes or sensitizes microglia and this appears to be the source of this amplified response. We will review the growing literature suggesting that a dysregulated neuroendocrine response in the aged organism is skewed toward higher brain CORT levels, and that this may play a critical role in priming microglia. Among the outcomes of an exaggerated neuroinflammatory response are impairments in synaptic plasticity, and reductions in key downstream mediators such as Arc and BDNF. We will show that each of these mechanisms is important for long-term memory formation, and is compromised by elevated pro-inflammatory cytokines.
健康的老年人在经历挑战性生活事件后，如严重细菌感染、手术或强烈的心理应激源，更有可能遭受严重的记忆障碍，而年轻人则不然。重要的是，这些外周挑战能够引发神经炎症反应（例如，促炎细胞因子增加）。在这篇综述中，我们将介绍文献证明，在健康的老年大脑中，这种反应被夸大和延长。正常衰老使小胶质细胞致敏或敏化，这似乎是这种放大反应的来源。我们将回顾越来越多的文献表明，衰老生物体中失调的神经内分泌反应偏向于大脑皮质醇水平升高，这可能在敏化小胶质细胞中发挥关键作用。神经炎症反应过度的结果之一是突触可塑性受损，以及关键下游介质如 Arc 和 BDNF 的减少。我们将表明，这些机制中的每一种对于长期记忆形成都很重要，并且会被升高的促炎细胞因子所损害。
