Abstract
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.
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Thanks to the Department of Pathophysiology of Hebei Medical university for providing some experimental sites.
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NM and PYL conceived and designed this work. NM performed the main experiments. MYS worked on the cigarette smoke exposure. YHD, TTH, XJ, and YNX analyzed the data. NM wrote the manuscript. All authors read and approved the final manuscript.
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All animal care and experimental procedures were approved by the Animal Care and Management Committee of Hebei General Hospital (Permit Number SCXK20160006).
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Meng, N., Dong, Y., Huo, T. et al. Past Exposure to Cigarette Smoke Aggravates Cognitive Impairment in a Rat Model of Vascular Dementia via Neuroinflammation. Cell Mol Neurobiol 42, 1021–1034 (2022). https://doi.org/10.1007/s10571-020-00992-2
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DOI: https://doi.org/10.1007/s10571-020-00992-2