Behavioral and Cognitive Performance Following Exposure to Second-Hand Smoke (SHS) from Tobacco Products Associated with Oxidative-Stress-Induced DNA Damage and Repair and Disruption of the Gut Microbiome

Abstract

Exposure to second-hand Smoke (SHS) remains prevalent. The underlying mechanisms of how SHS affects the brain require elucidation. We tested the hypothesis that SHS inhalation drives changes in the gut microbiome, impacting behavioral and cognitive performance as well as neuropathology in two-month-old wild-type (WT) mice and mice expressing wild-type human tau, a genetic model pertinent to Alzheimer’s disease mice, following chronic SHS exposure (10 months to ~30 mg/m3). SHS exposure impacted the composition of the gut microbiome as well as the biodiversity and evenness of the gut microbiome in a sex-dependent fashion. This variation in the composition and biodiversity of the gut microbiome is also associated with several measures of cognitive performance. These results support the hypothesis that the gut microbiome contributes to the effect of SHS exposure on cognition. The percentage of 8-OHdG-labeled cells in the CA1 region of the hippocampus was also associated with performance in the novel object recognition test, consistent with urine and serum levels of 8-OHdG serving as a biomarker of cognitive performance in humans. We also assessed the effects of SHS on the percentage of p21-labeled cells, an early cellular marker of senescence that is upregulated in bronchial cells after exposure to cigarette smoke. Nuclear staining of p21-labeled cells was more prominent in larger cells of the prefrontal cortex and CA1 hippocampal neurons of SHS-exposed mice than in sham-exposed mice, and there was a significantly greater percentage of labelled cells in the prefrontal cortex and CA1 region of the hippocampus of SHS than air-exposed mice, suggesting that exposure to SHS may result in accelerated brain aging through oxidative-stress-induced injury.

Global, regional, and national burden of ischemic heart disease attributable to secondhand smoke from 1990 to 2019

“…Harmful components in SHS, such as nicotine and carbon monoxide, impair vasodilatory function and increase the risk of atherosclerosis; simultaneously, oxidative stress and elevated markers of inflammation (e.g. C-reactive protein) induced by SHS further promote vascular pathology and thrombosis 5 , 6 . Additionally, SHS raises the risk of IHD by increasing blood viscosity and affects the autonomic nervous system, as evidenced by elevated heart rates and blood pressure 19 .…”

“…Our research findings underscore the imperative need to reinforce smoking control policies and diminish public exposure to SHS 28 . The comprehensive enforcement of indoor smoking bans and public education campaigns to elevate awareness of the hazards associated with SHS exposure constitutes a pivotal strategy for safeguarding public health and alleviating healthcare burdens 5 , 29 . Moreover, fostering smoke-free environments and providing readily accessible smoking cessation support services, such as counseling and nicotine replacement therapies, are crucial for facilitating smokers’ quitting efforts 20 , 30 .…”

“…Previous studies have explored the association between SHS and IHD 5 , 6 , yet limited research has evaluated the spatial and temporal trends of IHD burden attributable to SHS globally. This study comprehensively assesses the impact of SHS exposure on the IHD burden by analyzing data from 204 countries and regions from 1990 to 2019, aiming to provide a scientific basis for formulating effective public health policies and interventions to mitigate the deleterious effects of SHS on cardiovascular health.…”