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

• Published in: Translational psychiatry Vol. 9; no. 1; p. 159
• Main Authors: Frintrop, Linda, Trinh, Stefanie, Liesbrock, Johanna, Leunissen, Christina, Kempermann, Julia, Etdöger, Serhat, Kas, Martien J., Tolba, René, Heussen, Nicole, Neulen, Joseph, Konrad, Kerstin, Päfgen, Vera, Kiessling, Fabian, Herpertz-Dahlmann, Beate, Beyer, Cordian, Seitz, Jochen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.06.2019; Nature Publishing Group
• Subjects: 38/39; 38/77; 59/57; 631/378/340; 692/699/476; Animals; Anorexia; Anorexia Nervosa - diagnostic imaging; Anorexia Nervosa - etiology; Anorexia Nervosa - pathology; Astrocytes - cytology; Astrocytes - metabolism; Behavioral Sciences; Biological Psychology; Brain - cytology; Brain - diagnostic imaging; Brain - pathology; Brain research; Cerebral Cortex - diagnostic imaging; Cerebral Cortex - pathology; Corpus Callosum - diagnostic imaging; Corpus Callosum - pathology; Disease Models, Animal; Female; Magnetic Resonance Imaging; Medicine; Medicine & Public Health; Motor Activity - physiology; Neurosciences; Pharmacotherapy; Psychiatry; Rats; Rats, Wistar; Starvation - diagnostic imaging; Starvation - pathology
• ISSN: 2158-3188; 2158-3188
• DOI: 10.1038/s41398-019-0493-7

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.