Anorexia nervosa (AN) is a common chronic disease in adolescence and young adulthood. It is characterized by a dramatic body weight loss, an intense fear of gaining weight and a disturbed awareness of the own body. This psychiatric illness is associated with considerable brain volume reduction whereby the underlying pathophysiology of this volume loss and potential cellular changes in the brain following semi-starvation are not understood. The activity-based anorexia model (ABA) is an animal model representing many aspects of this psychiatric illness, including increased running activity, oestrous cycle disturbances and altered hormone production. Longitudinal magnetic resonance imaging (MRI) measurements revealed a total brain volume loss in the ABA group after starvation similar to that of AN patients and confirmed this using post mortem brain sections. Affected cells in the central nervous system (CNS) could be glia cells which are grouped in astrocytes, oligodendrocytes and microglia. Notably, the number of astrocytes but not neurons in gray and white matter was reduced in starved rats. These astrocytes fulfill various functions like provision of nutrients to the neurons, building the blood-brain barrier and modulating neuronal activity. After refeeding, the brain volume and the astrocyte reductions were mostly reinstated, well in line with patients’ brain volume findings. Reversible astrocyte loss underlying brain changes in AN could potentially be responsible for neuronal dysfunction and neuropsychological deficits typically found in acutely ill patients.

Our group is interested to understand the physiology and pathology of anorexia nervosa and its impact on the brain, especially the influence of glia cells in the complex process of food intake. Of note, astrocytes and microglia play active roles in feeding circuits in the hypothalamus, the center for regulating food intake. Therefore, glia cell changes and dysfunctions might contribute to the clinical symptoms of AN and thus are important new research targets for understanding and treating semi-starvation and AN. To answer our scientific questions, we use methods as design-based stereology, a set of behavioral analyses such as object recognition and open field tests, western blot and immunohistochemistry. Current research projects for students (medical doctor or bachelor/master thesis) are available.

Prof. Dr. Cordian Beyer and Dr. Stefanie Trinh, Department of Neuroanatomy, RWTH Aachen University, Germany

PD Dr. Jochen Seitz, Department of Child and Adolescent, Psychiatry, Psychosomatics and Psychotherapy, University Hospital, RWTH Aachen University, Germany

Prof. Dr. Kölch, Dr. Alexander Dück, PD Dr. Olaf Reis, Dr. Christoph Berger, Department for Child and Adolescent Psychiatry and Neurology, Rostock University Medical Center, Germany

Zimmermann A.*, Böge N.*, Schuster K., Staffeld A., Lang S., Gill S., Rupprecht H., Frintrop L. Glial cell changes in the corpus callosum in chronically-starved mice. (2023) Journal of Eating Disorders. PMID: 38111061

Staffeld A.*, Gill S.*, Zimmermann A., Böge N., Schuster K., Lang S., Kipp M., Palme R., Frintrop L. Establishment of a murine chronic anorexia nervosa model. (2023) Cells. PMID: 37443744

Gabloffsky T*, Gill S*, Staffeld A, Salomon R, Guerra N, Joost S, Hawlitschka A, Kipp M, Frintrop L. Food Restriction in Mice Induces Food-Anticipatory Activity and Circadian-Rhythm-Related Activity Changes. Nutrients (2022). PMID: 36558413.

Frintrop L, Trinh S,Seitz J, Kipp M. The Role of Glial Cells in Regulating Feeding Behavior: Potential Relevance to Anorexia Nervosa (2021). The Journal of Clinical Medicine. PMID: 35011927

Frintrop L*, Trinh S*, Liesbrock J, Leunissen C., Kempermann J, Etdöger S, Kas M, Tolba R, Heussen N, Neulen J, Konrad K, Päfgen V, Kiessling F, Herpertz-Dahlmann B, Beyer C, Seitz J. The reduction of astrocytes and brain volume loss in anorexia nervosa – the impact of starvation and refeeding in a rodent model. Translational Psychiatry (2019). PMID: 31164627

Frintrop L, Trinh S, Liesbrock J, Paulukat L, Kas M, Tolba R, Konrad K, Herpertz-Dahlmann B, Beyer C, Seitz J. Establishment of a chronic activity-based anorexia rat model. Journal of Neuroscience Methods (2018) PMID: 28970163

Frintrop L*, Liesbrock J*, Paulukat L, Johann S, Kas M, Tolba R, Heussen N, Neulen J, Konrad K, Herpertz-Dahlmann B, Beyer C, Seitz J. Reduced astrocyte density underlying brain volume reduction in activity-based anorexia rats. The World Journal of Biological Psychiatry (2018). PMID: 28132573

Paulukat L*, Frintrop L*, Liesbrock J, Heussen N, Johann S, Exner C, Kas M, Tolba R, Neulen J, Konrad K, Herpertz-Dahlmann B, Beyer C, Seitz J. Memory impairment is associated with the loss of regular estrous cycle and plasma estradiol levels in an activity-based anorexia animal model. The World Journal of Biological Psychiatry (2016). PMID: 27160428

FORUN-Programm UMR (Linda Frintrop): Astrozyten-Degeneration und Verhaltensdefizite in einem Modell der Anorexia nervosa

Doktor Robert Pfleger-Striftung (Linda Frintrop): Gliazell- und Verhaltensveränderung in einem murinen Modell der Anorexia nervosa