Reduced astrocyte density underlying brain volume reduction in activity-based anorexia rats

Abstract

Objectives: Severe grey and white matter volume reductions were found in patients with anorexia nervosa (AN) that were linked to neuropsychological deficits while their underlying pathophysiology remains unclear. For the first time, we analysed the cellular basis of brain volume changes in an animal model (activity-based anorexia, ABA).

Methods: Female rats had 24 h/day running wheel access and received reduced food intake until a 25% weight reduction was reached and maintained for 2 weeks.

Results: In ABA rats, the volumes of the cerebral cortex and corpus callosum were significantly reduced compared to controls by 6% and 9%, respectively. The number of GFAP-positive astrocytes in these regions decreased by 39% and 23%, total astrocyte-covered area by 83% and 63%. In neurons no changes were observed. The findings were complemented by a 60% and 49% reduction in astrocyte (GFAP) mRNA expression.

Conclusions: Volumetric brain changes in ABA animals mirror those in human AN patients. These alterations are associated with a reduction of GFAP-positive astrocytes as well as GFAP expression. Reduced astrocyte functioning could help explain neuronal dysfunctions leading to symptoms of rigidity and impaired learning. Astrocyte loss could constitute a new research target for understanding and treating semi-starvation and AN.

Keywords:

• ABA rat model
• anorexia nervosa
• astrocytes
• corpus callosum
• cortex volume

Acknowledgements

The present work was performed in (partial) fulfilment of the requirements for obtaining the degree ‘Dr. med.’/‘Dr. med. dent.’/‘Dr. rer. biol. hum’.

We would like to acknowledge the support of Mareike Schulz, Pascal Paschenda and Dr. Kira Scherer in the Institute for Laboratory Animal Science, Alexander Slowik, Helga Helten, Petra Ibold and Uta Zahn in the Institute of Neuroanatomy, and Dr. Cornelia Exner in the Department of Animal Physiology (Philipps-University Marburg, Marburg). This research was supported by the University Hospital Aachen, RWTH Aachen University, (START 108/12) and the Interdisciplinary Centre for Clinical Research, RWTH Aachen University (IZKF, N7-7/531440).

Disclosure statement

L. Frintrop, J. Liesbrock, L. Baumann, S. Johann, M. Kas, R. Tolba, N. Heussen, J. Neulen, K. Konrad, B. Herpertz-Dahlmann, C. Beyer and J. Seitz reported no conflicts of interest.

Additional information

Funding

University Hospital Aachen, RWTH Aachen University [START 108/12]; Interdisciplinary Centre for Clinical Research, RWTH Aachen University [IZKF, N7-7/531440].