Latham Amanda S, Moreno Julie A, Geer Charlize E
Department of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
Brain Research Center, Colorado State University, Fort Collins, CO, United States.
Front Aging. 2023 Aug 15;4:1244149. doi: 10.3389/fragi.2023.1244149. eCollection 2023.
Neuroinflammation is a universal characteristic of brain aging and neurological disorders, irrespective of the disease state. Glial inflammation mediates this signaling, through astrocyte and microglial polarization from neuroprotective to neurotoxic phenotypes. Glial reactivity results in the loss of homeostasis, as these cells no longer provide support to neurons, in addition to the production of chronically toxic pro-inflammatory mediators. These glial changes initiate an inflammatory brain state that injures the central nervous system (CNS) over time. As the brain ages, glia are altered, including increased glial cell numbers, morphological changes, and either a pre-disposition or inability to become reactive. These alterations induce age-related neuropathologies, ultimately leading to neuronal degradation and irreversible damage associated with disorders of the aged brain, including Alzheimer's Disease (AD) and other related diseases. While the complex interactions of these glial cells and the brain are well studied, the role additional stressors, such as infectious agents, play on age-related neuropathology has not been fully elucidated. Both biological agents in the periphery, such as bacterial infections, or in the CNS, including viral infections like SARS-CoV-2, push glia into neuroinflammatory phenotypes that can exacerbate pathology within the aging brain. These biological agents release pattern associated molecular patterns (PAMPs) that bind to pattern recognition receptors (PRRs) on glial cells, beginning an inflammatory cascade. In this review, we will summarize the evidence that biological agents induce reactive glia, which worsens age-related neuropathology.
神经炎症是大脑衰老和神经疾病的普遍特征，与疾病状态无关。神经胶质炎症通过星形胶质细胞和小胶质细胞从神经保护表型向神经毒性表型的极化来介导这种信号传导。神经胶质反应性导致体内平衡的丧失，因为这些细胞除了产生慢性毒性促炎介质外，不再为神经元提供支持。这些神经胶质变化引发一种炎症性脑状态，随着时间的推移会损害中枢神经系统（CNS）。随着大脑衰老，神经胶质会发生改变，包括神经胶质细胞数量增加、形态变化以及易于发生或无法发生反应。这些改变会诱发与年龄相关的神经病理学变化，最终导致神经元退化以及与老年脑疾病（包括阿尔茨海默病（AD）和其他相关疾病）相关的不可逆损伤。虽然这些神经胶质细胞与大脑之间的复杂相互作用已得到充分研究，但其他应激源（如病原体）在与年龄相关的神经病理学中所起的作用尚未完全阐明。外周的生物因子，如细菌感染，或中枢神经系统中的生物因子，包括像严重急性呼吸综合征冠状病毒2（SARS-CoV-2）这样的病毒感染，都会促使神经胶质细胞转变为神经炎症表型，从而加重衰老大脑中的病理变化。这些生物因子释放与模式相关的分子模式（PAMPs），它们与神经胶质细胞上的模式识别受体（PRRs）结合，引发炎症级联反应。在这篇综述中，我们将总结生物因子诱导反应性神经胶质细胞从而加重与年龄相关神经病理学变化的证据。
