School of Health and Biomedical Sciences, RMIT University, PO Box 71, Bundoora, VIC, 3083, Australia.
J Neuroinflammation. 2022 Mar 29;19(1):72. doi: 10.1186/s12974-022-02432-y.
Cigarette smoking (CS) is the leading cause of chronic obstructive pulmonary disease (COPD). The "spill-over" of pulmonary inflammation into the systemic circulation may damage the brain, leading to cognitive dysfunction. Cessation of CS can improve pulmonary and neurocognitive outcomes, however, its benefit on the neuroinflammatory profile remains uncertain. Here, we investigate how CS exposure impairs neurocognition and whether this can be reversed with CS cessation or an antioxidant treatment.
Male BALB/c mice were exposed to CS (9 cigarettes/day for 8 weeks) followed by 4 weeks of CS cessation. Another cohort of CS-exposed mice were co-administrated with a glutathione peroxidase mimetic, ebselen (10 mg/kg) or vehicle (5% CM-cellulose). We assessed pulmonary inflammation, spatial and working memory, and the hippocampal microglial, oxidative and synaptic profiles.
CS exposure increased lung inflammation which was reduced following CS cessation. CS caused spatial and working memory impairments which were attributed to hippocampal microglial activation and suppression of synaptophysin. CS cessation did not improve memory deficits or alter microglial activation. Ebselen completely prevented the CS-induced working and spatial memory impairments, which was associated with restored synaptophysin expression without altering microglial activation.
We were able to model the CS-induced memory impairment and microglial activation seen in human COPD. The preventative effects of ebselen on memory impairment is likely to be dependent on a preserved synaptogenic profile. Cessation alone also appears to be insufficient in correcting the memory impairment, suggesting the importance of incorporating antioxidant therapy to help maximising the benefit of cessation.
吸烟是慢性阻塞性肺疾病（COPD）的主要原因。肺部炎症向全身循环的“溢出”可能会损害大脑，导致认知功能障碍。戒烟可以改善肺部和神经认知结果，但它对神经炎症谱的益处仍不确定。在这里，我们研究吸烟如何损害神经认知，以及戒烟或抗氧化治疗是否可以逆转这种损害。
雄性 BALB/c 小鼠暴露于吸烟（每天 9 支香烟，持续 8 周），然后戒烟 4 周。另一组吸烟暴露的小鼠同时给予谷胱甘肽过氧化物酶模拟物，依布硒啉（10mg/kg）或载体（5% CM-纤维素）。我们评估了肺部炎症、空间和工作记忆以及海马小胶质细胞、氧化和突触谱。
吸烟暴露增加了肺部炎症，戒烟后炎症减少。吸烟导致空间和工作记忆障碍，这归因于海马小胶质细胞的激活和突触素的抑制。戒烟并未改善记忆缺陷或改变小胶质细胞的激活。依布硒啉完全预防了吸烟引起的工作和空间记忆障碍，这与恢复突触素表达有关，而不会改变小胶质细胞的激活。
我们能够模拟人类 COPD 中吸烟引起的记忆障碍和小胶质细胞激活。依布硒啉对记忆障碍的预防作用可能依赖于保持突触发生谱。单独戒烟似乎也不足以纠正记忆障碍，这表明抗氧化治疗的重要性，以帮助最大限度地发挥戒烟的益处。
