Anorexia Reduces GFAP+ Cell Density in the Rat Hippocampus

Abstract

Anorexia nervosa is an eating disorder observed primarily in young women. The neurobiology of the disorder is unknown but recently magnetic resonance imaging showed a volume reduction of the hippocampus in anorexic patients. Dehydration-induced anorexia (DIA) is a murine model that mimics core features of this disorder, including severe weight loss due to voluntary reduction in food intake. The energy supply to the brain is mediated by astrocytes, but whether their density is compromised by anorexia is unknown. Thus, the aim of this study was to estimate GFAP+ cell density in the main regions of the hippocampus (CA1, CA2, CA3, and dentate gyrus) in the DIA model. Our results showed that GFAP+ cell density was significantly reduced (~20%) in all regions of the hippocampus, except in CA1. Interestingly, DIA significantly reduced the GFAP+ cells/nuclei ratio in CA2 (−23%) and dentate gyrus (−48%). The reduction of GFAP+ cell density was in agreement with a lower expression of GFAP protein. Additionally, anorexia increased the expression of the intermediate filaments vimentin and nestin. Accordingly, anorexia increased the number of reactive astrocytes in CA2 and dentate gyrus more than twofold. We conclude that anorexia reduces the hippocampal GFAP+ cell density and increases vimentin and nestin expression.

Structural and functional changes in the central nervous system in the course of anorexia nervosa

“…Anorexia increased the number of reactive astrocytes in CA2 region and in the dentate gyrus more than two-fold. As indicated by the data presented in patients with anorexia nervosa, we observe a reduced density of GFAP + hippocampal cells and increased vimentin and nestin expression [13].…”

“…Brak łaknienia zwiększał liczbę reaktywnych astrocytów w regionie CA2 oraz w zakręcie zębatym ponad dwukrotnie. Jak wskazują przedstawione dane u chorych z jadłowstrętem psychicznym mamy do czynienia ze zmniejszoną gęstością komórek GFAP+ hipokampa i zwiększoną ekspresją wimentyny oraz nestyny [13].…”

Thirty years after anorexia nervosa onset, serum neurofilament light chain protein concentration indicates neuronal injury

“…Other studies have reported neurohistological abnormalities in individuals with AN and in AN animal models indicating degeneration associated with "pseudoatrophia cerebri". A postmortem study showed quantitative and qualitative changes in neuronal dendritic spine morphology [37], and animal studies using dehydration-induced, forced food-restricted, or activity-based AN models have found reduced astrocytes in the hippocampus, corpus callosum, and cerebral cortex [9,[38][39][40]. Future studies need to collect biomarkers from cerebral spinal fluid to investigate possible degenerative processes caused by AN in greater detail.…”

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

“…The best-established animal model that mimics the core symptoms of AN, such as weight loss, hyperactivity, and amenorrhea, is the so-called activity-based anorexia (ABA) paradigm 22 , which combines restricted food availability with access to a running wheel. This combination results in starvation and voluntary hyperactivity in ABA animals; this seemingly contradictory activity can possibly be explained as food seeking behavior and is driven by lower leptin levels 22,23 . We established a modified version of the original ABA model by giving a limited amount of food instead of a limited time for feeding with the aim of preventing mortality in the animals 24,25 .…”