Aktivitäts-basierte Anorexie ist ein Tiermodell für Anorexia nervosa

Anorexia nervosa (AN) in an eating disorder diagnosed by the occurrence of the ensuing symptoms: a strong wish to lose body weight, restricted caloric intake, a distorted body image, and hyperactivity. Despite the well-defined symptomatology of the disease, the pathophysiology still remains poorly explained. Moreover, a specific pharmacological treatment is lacking. In order to better characterize pathophysiological alterations occurring under disease conditions, animal models can be useful. The activity-based anorexia (ABA) model for rats mimics the disease by combining the two factors of restricted feeding (access to food: 1.5h/day) with the possibility of voluntary exercise in a running wheel installed in the rats’ cage. The aim of the studies was to investigate the modulation of food intake and body weight under conditions of ABA as well as to describe neuronal changes possibly underlying the observed alterations. Female Sprague-Dawley rats were used and randomly assigned to one of four groups: ad libitum (AL, ad libitum food, no running wheel, n=9), activity (AC, ad libitum food and running wheel, n=9), restricted feeding (RF, food restriction, no running wheel, n=12) and activity-based anorexia (ABA, food restriction and running wheel, n=11). Following validation of an automated food intake-monitoring system for the use in rats, food intake microstructure was assessed under conditions of ABA. ABA resulted in a pronounced body weight loss of -22% compared to the first day of food restriction (p0.05). An analysis of the neuronal changes showed that ABA leads to an activation of distinct brain nuclei involved in the regulation of food intake (LS, LHA, Arc, DMH, NTS), gastrointestinal motility (LHA, NTS, 10N), thermoregulation (DMH), circadian rhythm (DMH), stress (PVN, LC), memory (hippocampus) and depressiveness/anxiety (SON, PVN, DR, Rpa). Immunohistochemical doublestaining for c-Fos and the anorexigenic peptide nesfatin-1 -indicated by a significant increase of nesfatin-1 immunoreactive cells in PVN, DMH, Arc, LC and NTS in ABA rats (p0.05), noch in der Laufradaktivität (ABA vs. AC, p>0.05). Die Analyse der neuronalen Veränderungen ergab, dass ABA zu einer Aktivierung von Gehirngebieten führt, die in die Regulation von Nahrungsaufnahme (LS, LHA, Arc, DMH, NTS), gastrointestinaler Motilität (LHA, NTS, 10N), Thermoregulation (DMH), zirkadiane Rhythmen (DMH), Stress (PVN, LC), Gedächtnis (Hippocampus) und Depressivität/Angst (SO, PVN, DR, Rpa) involviert sind. Immunhistochemische Doppelfärbungen von c-Fos und dem anorexigenen Peptid Nesfatin-1 gaben Anlass zu der Vermutung, dass Nesfatin-1 eine Rolle bei ABA und eventuell auch bei Patienten mit AN spielt, denn Nesfatin-1 immunreaktive Zellen waren bei ABA-Tieren im PVN, DMH, Arc, LC und NTS (p