INTRODUCTION: Physical activity (PA) is widely associated with many health benefits e.g. due to effects on brain function. PA has been proposed as a behavioral intervention to counteract the neurotoxic effects of methamphetamine (METH). METH is one of the most popular psychostimulants in the world which contributes to neuroinflammation.

AIM(S): Here, we evaluate if different levels of PA affects inflammasome profile in the frontal cortices of adult female and male mice exposed to METH.

METHOD(S): Female (n=48) and male (n=48) C57BL/6 adult mice were divided into a control group injected with saline (Veh) and mice exposed for 5 days to METH. Then, mice were subjected to 14-days voluntary wheel running (VWR groups) or kept sedentary (SED). In VWR cohorts PA levels were identified post running period, based on the total distance covered, creating VWR-L, VWR-M and VWR-G groups (low-, moderate-, and good-runners, respectively). At the end of the experiment, cortical samples were collected. We evaluated the level of inflammasome proteins (NLRP1, NLRP3, NLRC4, pro-IL18 and IBA1) by using Western blot analysis.

RESULTS: We observed the significant effect of sex factor for distance covered and time spent in the wheel, showing that females were more active than males. The effect of PA was more pronounced in females, which was manifested in NLRC4 and pro-IL18, and showed a tendency in IBA1 and NLRP1. In females, the PA x METH interaction was revealed for IBA1. The effect of METH was noticed only in the level of pro-IL18 in females. In males, we observed the significant effect of the PA on the expression of IBA1 and the trend in NLRP3. Moreover, we found an interaction between PA and METH on the protein level of NLRP3.

CONCLUSIONS: The results demonstrate distinct inflammasome protein responses in the cortex on PA with different levels in METH-treated adult mice in sex-dependent manner.

FINANCIAL SUPPORT: The study was supported by the National Science Centre (NSC) grant 2019/35/B/NZ7/03155.