Aging is a complex biological process that increases the risk of age-related cognitive degenerative diseases such as dementia, including Alzheimer’s disease (AD), Lewy Body Dementia (LBD), and mild cognitive impairment (MCI). Even non-pathological aging of the brain can involve chronic oxidative and inflammatory stress, which disrupts the communication and balance between the brain and the immune system. There has been an increasingly strong connection found between chronic neuroinflammation and impaired memory, especially in AD. While microglia and astrocytes, the resident immune cells of the central nervous system (CNS), exerting beneficial effects during the acute inflammatory phase, during chronic neuroinflammation they can become more detrimental. Central cholinergic circuits are involved in maintaining normal cognitive function and regulating signaling within the entire cerebral cortex. While neuronal-glial cholinergic signaling is anti-inflammatory and anti-oxidative, central cholinergic neuronal degeneration is implicated in impaired learning, memory sleep regulation, and attention. Although there is evidence of cholinergic involvement in memory, fewer studies have linked the cholinergic anti-inflammatory and anti-oxidant pathways to memory processes during development, normal aging, and disease states. This review will summarize the current knowledge of cholinergic effects on microglia and astroglia, and their role in both anti-inflammatory and anti-oxidant mechanisms, concerning normal aging and chronic neuroinflammation. We provided details on how stimulation of α7 nicotinic acetylcholine (α7nACh) receptors can be neuroprotective by increasing amyloid-β phagocytosis, decreasing inflammation and reducing oxidative stress by promoting the nuclear factor erythroid 2-related factor 2 (Nrf2) pathways and decreasing the release of pro-inflammatory cytokines. There is also evidence for astroglial α7nACh receptor stimulation mediating anti-inflammatory and antioxidant effects by inhibiting the nuclear factor-κB (NF-κB) pathway and activating the Nrf2 pathway respectively. We conclude that targeting cholinergic glial interactions between neurons and glial cells via α7nACh receptors could regulate neuroinflammation and oxidative stress, relevant to the treatment of several neurodegenerative diseases.

衰老是一个复杂的生物过程，会增加与年龄有关的认知退化性疾病的风险，例如老年痴呆症，包括阿尔茨海默氏病（AD），路易体痴呆症（LBD）和轻度认知障碍（MCI）。即使是大脑的非病理性衰老，也可能涉及慢性氧化和炎症应激，这会破坏大脑与免疫系统之间的沟通和平衡。在慢性神经发炎和记忆力减退之间发现了越来越紧密的联系，尤其是在AD中。小胶质细胞和星形胶质细胞是中枢神经系统（CNS）的固有免疫细胞，在急性炎症阶段会发挥有益的作用，而在慢性神经炎症期间会变得更加有害。中央胆碱能回路参与维持正常的认知功能并调节整个大脑皮层内的信号传导。虽然神经胶质胆碱能信号传导抗炎和抗氧化，但中枢胆碱能神经元变性与学习，记忆睡眠调节和注意力受损有关。尽管有证据表明胆碱能参与记忆，但很少有研究将胆碱能抗炎和抗氧化途径与发育，正常衰老和疾病状态下的记忆过程联系起来。这篇综述将总结有关胆碱能对小胶质细胞和星形胶质细胞的影响的最新知识，以及它们在涉及正常衰老和慢性神经炎症的抗炎和抗氧化机制中的作用。我们提供了有关α7烟碱乙酰胆碱（α7nACh）受体刺激如何通过增加淀粉样蛋白-β吞噬作用，减少炎症和通过促进核因子红系2相关因子2（Nrf2）通路并减少氧化亚铁释放而对神经保护的详细信息。促炎细胞因子。也有证据表明星形胶质α7nACh受体刺激分别通过抑制核因子-κB（NF-κB）途径和激活Nrf2途径介导抗炎和抗氧化作用。我们得出结论，靶向神经元和神经胶质细胞之间的胆碱能神经胶质相互作用 通过促进核因子红系2相关因子2（Nrf2）通路并减少促炎性细胞因子的释放来减少炎症并降低氧化应激。也有证据表明星形胶质α7nACh受体刺激分别通过抑制核因子-κB（NF-κB）途径和激活Nrf2途径介导抗炎和抗氧化作用。我们得出结论，靶向神经元和神经胶质细胞之间的胆碱能神经胶质相互作用 通过促进核因子红系2相关因子2（Nrf2）通路并减少促炎性细胞因子的释放来减少炎症并降低氧化应激。也有证据表明星形胶质α7nACh受体刺激分别通过抑制核因子-κB（NF-κB）途径和激活Nrf2途径介导抗炎和抗氧化作用。我们得出结论，靶向神经元和神经胶质细胞之间的胆碱能神经胶质相互作用通过 α7nACh受体可以调节神经炎症和氧化应激，与几种神经退行性疾病的治疗有关。