Niraula Anzela, Sheridan John F, Godbout Jonathan P
Department of Neuroscience, The Ohio State University, Columbus, OH, USA.
Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA.
Neuropsychopharmacology. 2017 Jan;42(1):318-333. doi: 10.1038/npp.2016.185. Epub 2016 Sep 8.
The population of aged individuals is increasing worldwide and this has significant health and socio-economic implications. Clinical and experimental studies on aging have discovered myriad changes in the brain, including reduced neurogenesis, increased synaptic aberrations, higher metabolic stress, and augmented inflammation. In rodent models of aging, these alterations are associated with cognitive decline, neurobehavioral deficits, and increased reactivity to immune challenges. In rodents, caloric restriction and young blood-induced revitalization reverses the behavioral effects of aging. The increased inflammation in the aged brain is attributed, in part, to the resident population of microglia. For example, microglia of the aged brain are marked by dystrophic morphology, elevated expression of inflammatory markers, and diminished expression of neuroprotective factors. Importantly, the heightened inflammatory profile of microglia in aging is associated with a 'sensitized' or 'primed' phenotype. Mounting evidence points to a causal link between the primed profile of the aged brain and vulnerability to secondary insults, including infections and psychological stress. Conversely, psychological stress may also induce aging-like sensitization of microglia and increase reactivity to secondary challenges. This review delves into the characteristics of neuroinflammatory signaling and microglial sensitization in aging, its implications in psychological stress, and interventions that reverse aging-associated deficits.
全球老年人口数量正在增加，这具有重大的健康和社会经济影响。关于衰老的临床和实验研究发现，大脑中发生了无数变化，包括神经发生减少、突触畸变增加、代谢压力升高以及炎症加剧。在衰老的啮齿动物模型中，这些改变与认知能力下降、神经行为缺陷以及对免疫挑战的反应性增加有关。在啮齿动物中，热量限制和年轻血液诱导的恢复活力可逆转衰老的行为影响。老年大脑中炎症增加部分归因于小胶质细胞的常驻群体。例如，老年大脑的小胶质细胞具有营养不良的形态、炎症标志物表达升高以及神经保护因子表达减少的特征。重要的是，衰老过程中小胶质细胞炎症特征的增强与“致敏”或“预激”表型有关。越来越多的证据表明，老年大脑的预激状态与对包括感染和心理压力在内的二次损伤的易感性之间存在因果关系。相反，心理压力也可能诱导小胶质细胞出现类似衰老的致敏，并增加对二次挑战的反应性。本综述深入探讨了衰老过程中神经炎症信号传导和小胶质细胞致敏的特征、其在心理压力中的影响以及逆转与衰老相关缺陷的干预措施。
