Past Exposure to Cigarette Smoke Aggravates Cognitive Impairment in a Rat Model of Vascular Dementia via Neuroinflammation

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- 1 beta (IL-1 beta) pathway, and eucaryotic initiation factor 2 alpha (eIF2 alpha) /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-1 beta levels were detected by ELISA. The protein levels of NLRP3/caspase-1/ IL-1 beta and eIF2 alpha/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-1 beta pathway, and eIF2 alpha/autophagy pathway. Past exposure to cigarette smoke can also affect cognitive function by influencing neuroinflammation and NLRP3/caspase-1/IL-1 beta 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-1 beta, and eIF2 alpha/autophagy pathway and cognitive impairment induced by past exposure to cigarette smoke via neuroinflammation and NLRP3/caspase-1/IL-1 beta pathway. The combined group had the worst cognitive impairment because of harmful reasons.

Automated summary

Smoking is a risk factor for dementia, and quitting smoking can partially restore cognitive function but still below the level of never smokers. The effects of smoking cessation combined with cerebral chronic hypoperfusion on cognitive function have not been previously described.