Patterson Susan L
Temple University, Biology Life Science Building, 1900 N. 12th Street, Philadelphia, PA, 19122, USA.
Neuropharmacology. 2015 Sep;96(Pt A):11-8. doi: 10.1016/j.neuropharm.2014.12.020. Epub 2014 Dec 27.
Older individuals often experience declines in cognitive function after events (e.g. infection, or injury) that trigger activation of the immune system. This occurs at least in part because aging sensitizes the response of microglia (the brain's resident immune cells) to signals triggered by an immune challenge. In the aging brain, microglia respond to these signals by producing more pro-inflammatory cytokines (e.g. interleukin-1beta or IL-1β) and producing them for longer than microglia in younger brains. This exaggerated inflammatory response can compromise processes critical for optimal cognitive functioning. Interleukin-1β is central to the inflammatory response and is a key mediator and modulator of an array of associated biological functions; thus its production and release is usually very tightly regulated. This review will focus on the impact of dysregulated production of IL-1β on hippocampus dependent-memory systems and associated synaptic plasticity processes. The neurotrophin brain-derived neurotrophic factor (BNDF) helps to protect neurons from damage caused by infection or injury, and it plays a critical role in many of the same memory and hippocampal plasticity processes compromised by dysregulated production of IL-1β. This suggests that an exaggerated brain inflammatory response, arising from aging and a secondary immune challenge, may erode the capacity to provide the BDNF needed for memory-related plasticity processes at hippocampal synapses. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'.
在引发免疫系统激活的事件（如感染或损伤）后，老年人常出现认知功能下降。这种情况至少部分是因为衰老使小胶质细胞（大脑中的常驻免疫细胞）对免疫挑战触发的信号反应更加敏感。在衰老的大脑中，小胶质细胞对这些信号的反应是产生更多的促炎细胞因子（如白细胞介素-1β或IL-1β），并且产生这些细胞因子的时间比年轻大脑中的小胶质细胞更长。这种过度的炎症反应会损害对最佳认知功能至关重要的过程。白细胞介素-1β是炎症反应的核心，是一系列相关生物学功能的关键介质和调节因子；因此其产生和释放通常受到非常严格的调控。本综述将聚焦于IL-1β产生失调对海马体依赖性记忆系统及相关突触可塑性过程的影响。神经营养因子脑源性神经营养因子（BDNF）有助于保护神经元免受感染或损伤造成的损害，并且在许多因IL-1β产生失调而受损的相同记忆和海马体可塑性过程中发挥关键作用。这表明，由衰老和继发性免疫挑战引起的过度的脑部炎症反应，可能会削弱为海马体突触处与记忆相关的可塑性过程提供所需BDNF的能力。本文是名为“神经免疫学与突触功能”的特刊的一部分。
