Activity-based anorexia induces long-lasting peripheral and central dysregulation of the immune response

Background Anorexia nervosa (AN) is a life-threatening psychiatric disorder that mainly affects young females with clear symptomatology, but unknown etiology. AN core symptoms, i.e. food restriction and hyperactivity, induce severe and persistent multiorgan dysfunctions that also involves the immune system. However, little is known about its contribution in AN severity and maintenance. Methods Adolescent female rats were exposed to the combination of food restriction and wheel exercise (i.e. the activity-based anorexia (ABA) protocol). At the acute phase of the AN phenotype, after 5 days of induction, and after a 7-day bodyweight recovery period: flow cytometry analyses were performed in blood and bone marrow cell suspensions, whereas gene expression analyses in ventral and dorsal hippocampus. Results ABA rats showed decreased circulating CD45+ cells and a shift between B cells and granulocytes in the pool of total immune cells in the bone marrow both at the acute phase and after bodyweight recovery. Moreover, ABA induction caused hippocampal neuroinflammation, as shown by increased Tnf- a in the acute phase. Notably, this effect did not trigger early microglial activation, since Cd11b and Iba1 mRNA levels did not change; however, after recovery, microglial cells shifted towards an active state, increasing Cd11b and Iba1 expression, only in the ventral hippocampus. Conclusion These findings suggest that AN induction induces alterations in the medullary skewing of the innate immune arm, which in turn may cause severe and endurable dysfunctions at central level, thus linking the AN phenotype to immune system dysregulations. Sponsored by: Cariplo Foundation 2023-1003