The induction of the activity-based anorexia is associated to the modulation of neuroinflammatory and oxidative balance mediators in the rat prefrontal cortex

Anorexia nervosa (AN) is a life-threatening and complex psychiatric disorder characterized by altered body perception and the adoption of disturbed eating behavior and excessively exercising to reach the desired thinness. Reiteration of these habits leads to severe consequences for general and mental health, and the presence of psychiatric comorbidities makes this disorder one of those with the highest mortality rate. Although the exact molecular mechanisms underlying AN development have not been fully elucidated, clinical and preclinical data suggest the involvement of the immune system as well as of mediators of the redox balance, systems with an established role also in other psychiatric disorders. On these bases, aim of our study was to assess cerebral levels of specific mediators of neuroinflammation and redox balance by using the activity-based anorexia (ABA) model. After a period of acclimation and adaptation, adolescent Sprague-Dawley female rats were divided in four experimental groups to be exposed for 6 days to (1) a combination of food restriction and wheel activity (ABA group), (2) voluntary running wheel activity (EXE group), (3) food restriction (RESTR group), (4) normal maintenance procedure (CTRL group). During the whole experiments, running wheel activity and animal body-weight were constantly monitored. The animals were then euthanized, the prefrontal cortex rapidly dissected and frozen in dry ice for the subsequent molecular analyses. Specifically, by using real time RT-PCR, we measured the gene expression of cardinal markers of neuroinflammation including pro-inflammatory and anti-inflammatory cytokines as well as markers of microglia activation. Moreover, we assessed the mRNA levels of specific mediators of the antioxidant component of the redox machinery. We observed an overall reduction of neuroinflammation in the ABA group, as indicated by a significant decrease of the pro-inflammatory cytokines TNF-α and IL-1β, the inflammasome NLRP3, and the marker of microglia activation CD11b. Conversely, we found a significant increase of the mRNA levels for IL-6, whose dual role as pro- and anti-inflammatory cytokine is well-established. These effects were paralleled by the upregulation of the antioxidant enzymes GPX1, SRXN1 and MT1α. Our data clearly indicate that the induction of activity-based anorexia in adolescent female rats is associated with alteration of both mediators of inflammation and oxidative balance in the prefrontal cortex. In particular we found that animals in the ABA group were characterized by lower neuroinflammation and increased antioxidant response. Since our experimental paradigm mimics the early stage of this complex pathology, we may hypothesize that the observed changes are the result of an adaptive response to the ABA induction Accordingly, further studies aimed to evaluate long-term effects will be crucial to better understand the molecular impact of ABA in the brain.