Evaluation of the leptin signaling in adolescent female rats exposed to the Activity-Based Anorexia model: focus on dorsal and ventral hippocampus

Background: Anorexia nervosa (AN) is a life-threatening disease characterised by self-imposed starvation and excessive exercise, predominantly affecting young females. Despite AN etiology is still unknown, a leading neurobiological hypothesis suggests potential dysregulations of appetite modulators, including the adipokine leptin. Specifically, AN patients show a correlation among hypoleptinemia and hyperactivity. However, it is still undetermined how the maintenance of AN behavior may be sustained by the leptin receptor (LepR) and its JAK2-STAT3 downstream pathway in the dorsal (dHip) and ventral (vHip) hippocampus, brain subregions involved in memory and learning processes. Methods: We exposed adolescent female rats to a combination of food restriction and to an activity wheel, i.e. the activity-based anorexia (ABA) model. Leptin plasma levels were determined by ELISA assay, while protein levels by Western Blot analysis. Spatial Order Object Recognition Test (SOR) was performed to test hippocampal functionality. Results: In ABA animals, leptin plasma levels were reduced at the acute phase of the condition [post-natal day (PND)42], while increased after a seven-day period of body-weight recovery (PND49). The LepR- JAK2-STAT3 pathway activation in dHip was reduced in ABA rats at both time points, while it underwent a shift from hypo- (PND42) to hyper-activation (PND49) in vHip. In addition, ABA rats demonstrated spatial cognitive impairment in the SOR test at both timepoints. Conclusions: Our findings suggest a potential correlation among fluctuation of leptin levels, AN phenotype, and hippocampal-dependent cognitive impairments that might pave the way for vulnerability to comorbid mental disorders, which frequently occur in AN patients. Sponsored by: PRIN P2022E4MLS