Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA.
J Neuroimmune Pharmacol. 2012 Mar;7(1):7-23. doi: 10.1007/s11481-011-9313-4. Epub 2011 Sep 20.
A hallmark of the aged immune system is impaired immunoregulation of the innate and adaptive immune system in the periphery and also in the central nervous system (CNS). Impaired immunoregulation may predispose older individuals to an increased frequency of peripheral infections with concomitant cognitive and behavioral complications. Thus, normal aging is hypothesized to alter the highly coordinated interactions between the immune system and the brain. In support of this notion, mounting evidence in rodent models indicate that the increased inflammatory status of the brain is associated with increased reactivity of microglia, the innate immune cells of the CNS. Understanding how immunity is affected with age is important because CNS immune cells play an integral role in propagating inflammatory signals that are initiated in the periphery. Increased reactivity of microglia sets the stage for an exaggerated inflammatory cytokine response following activation of the peripheral innate immune system that is paralleled by prolonged sickness, depressive-like complications and cognitive impairment. Moreover, amplified neuroinflammation negatively affects several aspects of neural plasticity (e.g., neurogenesis, long-term potentiation, and dendritic morphology) that can contribute to the severity of neurological complications. The purpose of this review is to discuss several key peripheral and central immune changes that impair the coordinated response between the immune system and the brain and result in behavioral and cognitive deficits.
衰老免疫系统的一个特点是，在外周和中枢神经系统（CNS）中，先天和适应性免疫系统的免疫调节受损。免疫调节受损可能使老年人更容易发生外周感染，并伴有认知和行为并发症。因此，人们假设正常衰老会改变免疫系统和大脑之间高度协调的相互作用。支持这一观点的是，越来越多的啮齿动物模型证据表明，大脑的炎症状态增加与中枢神经系统先天免疫细胞小胶质细胞的反应性增加有关。了解免疫随年龄的变化很重要，因为中枢神经系统免疫细胞在传播在外周起始的炎症信号中发挥着重要作用。小胶质细胞的反应性增强为外周先天免疫系统激活后炎症细胞因子反应过度奠定了基础，这与疾病持续时间延长、抑郁样并发症和认知障碍相平行。此外，神经炎症的放大对神经可塑性的几个方面（如神经发生、长时程增强和树突形态）产生负面影响，这可能导致神经并发症的严重程度增加。本综述的目的是讨论几个关键的外周和中枢免疫变化，这些变化会损害免疫系统和大脑之间的协调反应，导致行为和认知缺陷。
