Dobric Aleksandar, De Luca Simone N, Seow Huei Jiunn, Wang Hao, Brassington Kurt, Chan Stanley M H, Mou Kevin, Erlich Jonathan, Liong Stella, Selemidis Stavros, Spencer Sarah J, Bozinovski Steven, Vlahos Ross
School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia.
Front Mol Neurosci. 2022 May 17;15:893083. doi: 10.3389/fnmol.2022.893083. eCollection 2022.
Neurocognitive dysfunction is present in up to ∼61% of people with chronic obstructive pulmonary disease (COPD), with symptoms including learning and memory deficiencies, negatively impacting the quality of life of these individuals. As the mechanisms responsible for neurocognitive deficits in COPD remain unknown, we explored whether chronic cigarette smoke (CS) exposure causes neurocognitive dysfunction in mice and whether this is associated with neuroinflammation and an altered neuropathology.
Male BALB/c mice were exposed to room air (sham) or CS (9 cigarettes/day, 5 days/week) for 24 weeks. After 23 weeks, mice underwent neurocognitive tests to assess working and spatial memory retention. At 24 weeks, mice were culled and lungs were collected and assessed for hallmark features of COPD. Serum was assessed for systemic inflammation and the hippocampus was collected for neuroinflammatory and structural analysis.
Chronic CS exposure impaired lung function as well as driving pulmonary inflammation, emphysema, and systemic inflammation. CS exposure impaired working memory retention, which was associated with a suppression in hippocampal microglial number, however, these microglia displayed a more activated morphology. CS-exposed mice showed changes in astrocyte density as well as a reduction in synaptophysin and dendritic spines in the hippocampus.
We have developed an experimental model of COPD in mice that recapitulates the hallmark features of the human disease. The altered microglial/astrocytic profiles and alterations in the neuropathology within the hippocampus may explain the neurocognitive dysfunction observed during COPD.
高达约61%的慢性阻塞性肺疾病（COPD）患者存在神经认知功能障碍，其症状包括学习和记忆缺陷，对这些患者的生活质量产生负面影响。由于COPD中神经认知缺陷的机制尚不清楚，我们探讨了长期接触香烟烟雾（CS）是否会导致小鼠神经认知功能障碍，以及这是否与神经炎症和神经病理学改变有关。
将雄性BALB/c小鼠暴露于室内空气（假暴露组）或CS（每天9支香烟，每周5天）中24周。在23周后，对小鼠进行神经认知测试以评估工作记忆和空间记忆保持能力。在24周时，处死小鼠并收集肺组织，评估COPD的标志性特征。检测血清中的全身炎症水平，并收集海马进行神经炎症和结构分析。
长期接触CS损害了肺功能，并引发了肺部炎症、肺气肿和全身炎症。CS暴露损害了工作记忆保持能力，这与海马小胶质细胞数量的减少有关，然而，这些小胶质细胞呈现出更活化的形态。接触CS的小鼠海马中星形胶质细胞密度发生变化，同时突触素和树突棘减少。
我们建立了一种小鼠COPD实验模型，该模型概括了人类疾病的标志性特征。海马中微胶质细胞/星形胶质细胞特征的改变以及神经病理学的改变可能解释了COPD期间观察到的神经认知功能障碍。
