Department of Neurology, Hebei Medical University, No. 361 Zhongshan East Road, Changan District, Shijiazhuang, 050017, Hebei Province, People's Republic of China.
Department of Neurology, Hebei General Hospital, No. 348 Heping West Road, Xinhua District, Shijiazhuang, 050051, Hebei Province, People's Republic of China.
Cell Mol Neurobiol. 2022 May;42(4):1021-1034. doi: 10.1007/s10571-020-00992-2. Epub 2020 Nov 6.
Smoking is a risk factor for dementia. Cognitive function can be partially restored after quitting smoking, but still lower than never smoked group. The underlying mechanisms still remain unclear. The effects of smoking cessation combined with cerebral chronic hypoperfusion (CCH) on cognitive function have never been described. Here, we established a cigarette smoking cessation model, a CCH model, and a cigarette smoking cessation plus CCH model. We investigated cognitive function in these models and the mechanisms of the neuroinflammation, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)/cysteine aspartate-specific proteinase (caspase-1)/interleukin- 1β (IL-1β) pathway, and eucaryotic initiation factor 2α (eIF2α) /autophagy pathway. We used morris water maze (MWM) and novel object recognition (NOR) test to evaluate cognitive function in rats. Nissl staining was performed to observe cell morphology in the hippocampal CA1 area. A neuroinflammatory marker (glial fibrillary acidic protein, GFAP) was assessed by Western blot analysis and immunohistochemistry staining. IL-1β levels were detected by ELISA. The protein levels of NLRP3/caspase-1/ IL-1β and eIF2α/autophagy pathway were evaluated by Western blot analysis. LC3 was assessed by immunofluorescence staining. CCH can affect cognitive function by influencing neuroinflammation, NLRP3/caspase-1/IL-1β pathway, and eIF2α/autophagy pathway. Past exposure to cigarette smoke can also affect cognitive function by influencing neuroinflammation and NLRP3/caspase-1/IL-1β pathway, which may be induced by smoking and may not be alleviated after smoking cessation. Past exposure to cigarette smoke does not influence autophagy, which may be increased by smoking and then decrease to normal levels after smoking cessation. Past exposure to smoking can further aggravate cognitive impairment and neuroinflammation in VaD animals: cognitive impairment induced by CCH via neuroinflammation, NLRP3/caspase-1/IL-1β, and eIF2α/autophagy pathway and cognitive impairment induced by past exposure to cigarette smoke via neuroinflammation and NLRP3/caspase-1/IL-1β pathway. The combined group had the worst cognitive impairment because of harmful reasons.
吸烟是痴呆的一个危险因素。戒烟后认知功能可部分恢复，但仍低于从不吸烟组。其潜在机制尚不清楚。吸烟与脑慢性低灌注（CCH）联合对认知功能的影响尚未被描述。在这里，我们建立了一个戒烟模型、一个 CCH 模型和一个戒烟加 CCH 模型。我们在这些模型中研究了认知功能，以及神经炎症、核苷酸结合寡聚结构域样受体家族富含亮氨酸重复序列蛋白 3（NLRP3）/半胱氨酸天冬氨酸特异性蛋白酶-1（caspase-1）/白细胞介素-1β（IL-1β）通路和真核起始因子 2α（eIF2α）/自噬通路的机制。我们使用 Morris 水迷宫（MWM）和新物体识别（NOR）测试来评估大鼠的认知功能。通过尼氏染色观察海马 CA1 区细胞形态。通过 Western blot 分析和免疫组化染色评估神经炎症标志物（胶质纤维酸性蛋白，GFAP）。通过 ELISA 检测 IL-1β 水平。通过 Western blot 分析评估 NLRP3/caspase-1/IL-1β和 eIF2α/自噬通路的蛋白水平。通过免疫荧光染色评估 LC3。CCH 可通过影响神经炎症、NLRP3/caspase-1/IL-1β通路和 eIF2α/自噬通路来影响认知功能。既往吸烟也可通过影响神经炎症和 NLRP3/caspase-1/IL-1β通路来影响认知功能，这种影响可能是由吸烟引起的，戒烟后可能不会缓解。既往吸烟不会影响自噬，自噬可能会因吸烟而增加，然后在戒烟后恢复正常水平。既往吸烟会进一步加重 VaD 动物的认知障碍和神经炎症：CCH 通过神经炎症、NLRP3/caspase-1/IL-1β 和 eIF2α/自噬通路引起的认知障碍，以及既往吸烟通过神经炎症和 NLRP3/caspase-1/IL-1β 通路引起的认知障碍。由于有害原因，联合组的认知障碍最严重。
