Linda Frintrop1, Johanna Liesbrock1,2, Lisa Paulukat1,2, Sonja Johann1, Martien J Kas3,4, Rene Tolba5, Nicole Heussen6, Joseph Neulen7, Kerstin Konrad2, Beate Herpertz-Dahlmann2, Cordian Beyer1, Jochen Seitz2. 1. a Institute of Neuroanatomy, University Hospital, RWTH Aachen University , Aachen , Germany. 2. b Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy , University Hospital, RWTH Aachen University , Aachen , Germany. 3. c Department of Translational Neuroscience , Brain Center Rudolf Magnus, University Medical Center Utrecht , Utrecht , The Netherlands. 4. d Groningen Institute for Evolutionary Life Sciences, University of Groningen , the Netherlands. 5. e Institute for Laboratory Animal Science and Experimental Surgery , University Hospital, RWTH Aachen University , Aachen , Germany. 6. f Department of Medical Statistics , University Hospital Aachen, RWTH Aachen University , Aachen , Germany. 7. g Department of Gynecological Endocrinology and Reproductive Medicine , University Hospital, RWTH Aachen University , Aachen , Germany.
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.
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 ABArats, 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.
Entities:
Keywords:
ABA rat model; anorexia nervosa; astrocytes; corpus callosum; cortex volume
Authors: T Lee Gilman; W Anthony Owens; Christina M George; Lauren Metzel; Melissa Vitela; Livia Ferreira; Melodi A Bowman; Georgianna G Gould; Glenn M Toney; Lynette C Daws Journal: J Pharmacol Exp Ther Date: 2019-09-03 Impact factor: 4.030