Abstract
Growing evidence indicates that thirdhand smoke (THS) exposure induces many adverse health effects. However, it is unclear how THS exposure affects behavior and how host genetic background modulates phenotypic changes. Here we used the Collaborative Cross (CC) mouse population-based model to assess behavioral alterations immediately after THS exposure from 4 to 9 weeks of age. We first measured anxiety-like behavior in six strains using light/dark box combined with a custom multivariate mouse tracking system. We developed an anxiety risk scoring system based on anxiety-related traits and then evaluated the THS impact on them. THS exposure significantly decreased anxiety risk in CC019 (P = 0.002) and CC051 (P = 0.009), but increased anxiety risk in CC036 (P < 0.001), while the other three strains did not show significant changes in anxiety-related traits. Such differences were driven by female mice for the six measures of anxiety-like behavior. Memory potential was measured in the same cohort of mice using the passive avoidance assay. Both THS-exposed male and female CC019 mice displayed significant memory loss compared to controls while no significant changes were found in the other five strains. This study provides strong evidence that THS exposure leads to strain-dependent changes in anxiety-like behavior and memory, suggesting that host genetic variations play a critical role in individual susceptibility to THS-induced effects.
Highlights
Growing evidence indicates that thirdhand smoke (THS) exposure induces many adverse health effects
A computational p ipeline[27] was deployed to quantify six anxiety-like phenotypes extracted from each video file: latency time to enter the dark box for the first time, number of partial transitions, traveling distance in light, number of full transitions, total time in the light compartment, and average speed in light, where some of these phenotypes, e.g., time spent in light chamber, number of full transitions, and latency to enter the dark box, are frequently used to quantify mouse anxiety levels[35,36,37]
THS exposure significantly decreased anxiety risk in CC019 (P = 0.002) and CC051 (P = 0.009) mice (Fig. 3B,F), whereas THS exposure significantly increased risk of anxiety in CC036 mice (P < 0.001, Fig. 3C) in comparison to their corresponding control mice. These findings strongly suggest that the effects of THS exposure at young age on anxiety-like behavior are significantly modulated by host genetics and sex, and that THS exposure can lead to opposite effects in different genetic backgrounds
Summary
Growing evidence indicates that thirdhand smoke (THS) exposure induces many adverse health effects It is unclear how THS exposure affects behavior and how host genetic background modulates phenotypic changes. THS exposure significantly decreased anxiety risk in CC019 (P = 0.002) and CC051 (P = 0.009), but increased anxiety risk in CC036 (P < 0.001), while the other three strains did not show significant changes in anxiety-related traits Such differences were driven by female mice for the six measures of anxiety-like behavior. Small children may gain more exposure than adults because their age-related behaviors bring them in close contact with surfaces and dust contaminated with THS toxins Their physiological characteristics such as lower capacity to metabolize the toxins and high toxins/body weight ratio potentially make them more sensitive to adverse health effects associated with THS exposure. These observations warrant further investigations into the effects of THS exposure on other behavioral endpoints
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