Effects of Chronic Nicotine Exposure on Pathology in Alzheimer's Disease Model Mice
Objective To investigate the effects of different doses of chronic nicotine exposure on the pathology of Alzhei-mer's disease(AD),to clarify the effects of nicotine on cognitive function and related pathology in AD model mice,and to pro-vide laboratory evidence for clinical prevention and intervention of AD.Methods Nine-month-old triple-transgenic(3 × Tg)mice(APPswe,PS1M146V,and Tau P301L transgenes)were treated with low(5％,50 μg/mL),medium(10％,100 μg/mL)and high(20％,200 μg/mL)doses of nicotine for 3 months.Western blot,immunofluorescence and qPCR were used to detect amyloid be-ta(Aβ)pathology,Tau phosphorylation,synaptic damage and neuroinflammation in different groups of mice.Microglia was co-stained with Aβ to show the phagocytosis of plaques.Behavioral test was used to detect the cognitive learning ability of experi-mental mice.Results Administration of high dosage of nicotine over the course of three consecutive months resulted in an aug-mentation in Aβ plaques,while the utilization of low dosage of nicotine for an equivalent period yields a mitigating influence on Aβ accumulation and effectively alleviated synaptic impairments within the hippocampus.Moreover,chronic exposure of high nicotine exacerbated both microglial activation and neuroinflammation,along with astrogliosis in the brains of 3 X Tg mice,whereas the administration of low dosage of nicotine exhibited no discernible impact.Chronic exposure to different doses of nico-tine had no significant effect on Tau phosphorylation and cognitive behaviors in mice.Conclusion Chronic exposure to low dose nicotine alleviates Aβ accumulation and brain synaptic damage in AD model mice.Chronic exposure to high dose nicotine aggra-vates Aβ deposition and neuroinflammation.
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