The reduction of astrocytes and brain volume loss in anorexia nervosa\u2014the impact of starvation and refeeding in a rodent model

Linda Frintrop,Serhat Etdöger,Kerstin Konrad,Cordian Beyer,Martien J Kas,Fabian Kiessling,Julia Kempermann,Joseph Neulen,Beate Herpertz-Dahlmann,Jochen Seitz,Johanna Liesbrock,René Tolba,Vera Päfgen,Stefanie Trinh,Christina Leunissen,Nicole Heussen

doi:10.1038/s41398-019-0493-7

Abstract

Anorexia nervosa (AN) is an often chronic, difficult to treat illness that leads to brain volume reductions in gray and white matter. The underlying pathophysiology is poorly understood, despite its potential importance in explaining the neuropsychological deficits and clinical symptoms associated with the illness. We used the activity-based anorexia model (ABA), which includes food reduction and running wheel access in female rats to study brain changes after starvation and refeeding. Longitudinal animal MRI and post-mortem brain sections confirmed a reduction in the mean brain volumes of ABA animals compared to controls. In addition, the mean number of astrocytes was reduced by over 50% in the cerebral cortex and corpus callosum, while the mean number of neurons was unchanged. Furthermore, mean astrocytic GFAP mRNA expression was similarly reduced in the ABA animals, as was the mean cell proliferation rate, whereas the mean apoptosis rate did not increase. After refeeding, the starvation-induced effects were almost completely reversed. The observation of the astrocyte reduction in our AN animal model is an important new finding that could help explain starvation-induced neuropsychological changes in patients with AN. Astrocyte-targeted research and interventions could become a new focus for both AN research and therapy.

Highlights

Anorexia nervosa (AN) is the third most common chronic disease in adolescents, with the highest mortality rate of any mental illness[1]
The mean food intake and mean body weight of both cohorts are depicted in Fig. 1 (RWA in Supplementary Fig. 1)
The quality of the histological slides that were used for the histological volume detection was adequate for the analysis of the cortex and the corpus callosum

Summary

Introduction

Anorexia nervosa (AN) is the third most common chronic disease in adolescents, with the highest mortality rate of any mental illness[1]. It is characterized by a combination of insufficient energy intake and often increased physical activity that results in severe weight loss[2,3]. Medical intervention is very limited, and there is no approved pharmacological treatment available for patients. Frintrop et al Translational Psychiatry (2019)9:159 changes appear to be reversible[7,14]. Chronically underweight patients seem to have progressive brain changes[15]. The underlying pathomechanism of this brain volume reduction in AN is largely unknown.

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