Reduced hypothalamic [³H]PK11195 binding in Lewis rats after chronic high-intensity interval training

Exercise has emerged as a potential adjunctive intervention for mood-, trauma-, anxiety-, and addictive disorders, partly through effects on neuroimmune signaling. However, it remains unclear whether chronic high-intensity interval training (HIIT) alters translocator protein 18 kDa (TSPO)-associated neuroimmune activity across brain regions. This study examined the effects of chronic HIIT on [³H]PK11195 binding in male and female Lewis rats.

Thirty-one Lewis rats were assigned to either a 6-week HIIT treadmill regimen or a sedentary control condition. Twenty-four hours after the final session, brains were collected for [³H]PK11195 autoradiography, and specific binding was quantified across multiple cortical and subcortical regions of interest. Binding in each region was analyzed using two-way ANOVA with exercise and sex as factors.

A significant main effect of exercise was observed in the hypothalamus, with the HIIT exercise rats showing 28% lower [³H]PK11195 binding than sedentary controls. Also, there was a significant main effect of sex in the visual cortex, with females showing higher binding than males.

Chronic HIIT exercise was associated with a potential exercise-related modulation of TSPO-associated neuroimmune signaling in the hypothalamus reflected in region-specific reductions in [³H]PK11195 binding, an indirect index of TSPO-associated neuroimmune signaling that should not be equated with direct evidence of reduced microglial activation. Moreover, TSPO-associated neuroimmune signaling may vary by sex in a region-dependent manner. The observed hypothalamic association warrants future studies testing whether changes in TSPO-associated signaling are linked to functional outcomes in stress, reward, or neuropsychiatric models.