小鼠青春期香烟暴露通过前额叶小胶质细胞 介导的炎症反应影响成年后学习记忆功能

AIM: To investigate the effects of cigarette smoke exposure during adolescence on the inflammatory response mediated by microglia in the prefrontal cortex of mice, and its impact on learning and memory functions in adulthood. METHODS: 72 two-week-old healthy male Kunming mice, with each weighing (11. 0±1. 5) g, were randomly divided into control and cigarette exposure groups (n=36 per group). The mice in the cigarette exposure group were passively exposed to 6 cigarettes daily for 10 weeks. At three time points of 4-week-old (infancy), 8-week-old (adolescence), and 12-week-old(adulthood), six mice were selected from each group to have their neurobehavioral and pathological changes examined. In particular, the step-down test, three-chamber social interaction test, and novel object recognition test were used to detect changes in learning and memory abilities and cognitive behavior. Immunofluorescence testing was performed to detect the morphology, number of synapses, and expression of inflammatory factor apoptosis-associated speck-like protein containing a CARD (ASC) around the microglial cells in the prefrontal cortex of mice in each group. Western blot was performed to assess the expression levels of synaptophysin (SYP) and postsynaptic density protein-95 (PSD-95) in the cerebral cortex of mice in each group. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the protein expression of tumor necrosis factor-α(TNF-α), interleukin 1β(IL-1β), and IL-6 in the prefrontal cortex. RESULTS: (1) In the step-down test, the latency of mice at 8 and 12 weeks of age was significantly shortened, and the number of errors was significantly increased in the cigarette exposure group compared with the age-matched control group (P<0. 01). In addition, the social recognition time and exploration time for novel objects were prolonged (P< 0. 05).(2) Immunofluorescence assays revealed that exposure to cigarette smoke in mice, at both 8 and 12 weeks of age, resulted in a reduction of SYP-positive puncta within the prefrontal cortex. Concurrently, there was an observed increase in the number of Iba1-positive microglia, which exhibited an activated phenotype, as well as an elevation in ASC-positive puncta in proximity to the microglia. Western blot further revealed reduced expression of synaptophysin protein SYP and PSD-95 in the cerebral cortex of the mice at 8 and 12 weeks of age in the cigarette exposure group (P<0. 05). (3) ELISA showed increased levels of inflammatory factors TNF-α, IL-1β, and IL-6 in the prefrontal cortex of the mice at 8 and 12 weeks of age in the cigarette exposure group (P<0. 05). CONCLUSION: Exposure to cigarette smoke during adolescence in mice may result in the enhanced secretion of inflammatory factors through the activation of microglia in the prefrontal cortex. This activation can alter microglial function and induce synaptic damage, consequently impairing learning, memory, and cognitive abilities in adulthood. [ABSTRACT FROM AUTHOR]