Immune and behavioral consequences of microglial reactivity in the aged brain.
Immune and behavioral consequences of microglial reactivity in the aged brain.
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衰老大脑中小胶质细胞反应的免疫和行为后果。
DOI：
10.1093/icb/icp009
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发表时间：
2009
影响因子：
2.6
通讯作者：
Godbout,JonathanP
中科院分区：
文献类型：
--
作者：
Wynne,AngelaM;Henry,ChristopherJ;Godbout,JonathanP
免疫系统和大脑之间的双向通信对于对免疫激活进行适当的免疫、生理和行为反应至关重要。然而，衰老可能会削弱这种重要的双向相互作用。为了支持这一观点，老年人外周感染与行为和认知并发症的频率增加有关。最近在衰老和神经退行性疾病的动物模型中的发现表明，小胶质细胞，大脑的先天免疫细胞，变得启动或反应。了解小胶质细胞中与年龄和疾病相关的改变是很重要的，因为胶质细胞（小胶质细胞和星形胶质细胞）在传播外周启动的炎症信号中起着不可或缺的作用。在这种能力下，脑胶质细胞产生靶向神经元底物的炎性细胞因子，并引发通常对宿主生物体有益的疾病-行为综合征。小胶质细胞的反应性增加为外周先天免疫系统激活后过度的神经炎性细胞因子反应奠定了基础，这可能是随后持久的行为和认知缺陷的基础。为了支持这一前提，最近的研究结果表明，刺激老年啮齿动物的外周免疫系统会导致过度的神经炎症，这会导致认知障碍、长期疾病和抑郁样并发症。因此，本综述的目的是讨论新的证据表明，年龄相关的小胶质细胞启动可能发挥了夸张的行为和认知后遗症外周感染的病理生理作用。
Bidirectional communication between the immune system and the brain is essential for mounting the appropriate immunological, physiological, and behavioral responses to immune activation. Aging, however, may impair this important bi-directional interaction. In support of this notion, peripheral infection in the elderly is associated with an increased frequency of behavioral and cognitive complications. Recent findings in animal models of aging and neurodegenerative disease indicate that microglia, innate immune cells of the brain, become primed or reactive. Understanding age- and disease-associated alterations in microglia is important because glia (microglia and astrocytes) play an integral role in propagating inflammatory signals that are initiated in the periphery. In this capacity, brain glia produce inflammatory cytokines that target neuronal substrates and elicit a sickness-behavior syndrome that is normally beneficial to the host organism. Increased reactivity of microglia sets the stage for an exaggerated neuroinflammatory cytokine response following activation of the peripheral innate immune system, which may underlie subsequent long-lasting behavioral and cognitive deficits. In support of this premise, recent findings indicate that stimulation of the peripheral immune system in aged rodents causes exaggerated neuroinflammation that is paralleled by cognitive impairment, prolonged sickness, and depressive-like complications. Therefore, the purpose of this review is to discuss the new evidence that age-associated priming of microglia could play a pathophysiological role in exaggerated behavioral and cognitive sequelae to peripheral infection.