Dehydration-Induced Anorexia Reduces Astrocyte Density in the Rat Corpus Callosum

Abstract

Anorexia nervosa is an eating disorder associated with severe weight loss as a consequence of voluntary food intake avoidance. Animal models such as dehydration-induced anorexia (DIA) mimic core features of the disorder, including voluntary reduction in food intake, which compromises the supply of energy to the brain. Glial cells, the major population of nerve cells in the central nervous system, play a crucial role in supplying energy to the neurons. The corpus callosum (CC) is the largest white matter tract in mammals, and more than 99% of the cell somata correspond to glial cells in rodents. Whether glial cell density is altered in anorexia is unknown. Thus, the aim of this study was to estimate glial cell density in the three main regions of the CC (genu, body, and splenium) in a murine model of DIA. The astrocyte density was significantly reduced (~34%) for the DIA group in the body of the CC, whereas in the genu and the splenium no significant changes were observed. DIA and forced food restriction (FFR) also reduced the ratio of astrocytes to glial cells by 57.5% and 22%, respectively, in the body of CC. Thus, we conclude that DIA reduces astrocyte density only in the body of the rat CC.

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

“…The results fit well with those of the proof-of-concept study, which pointed to an astrocyte reduction in ABA rats 26 and with those of studies by Reyes-Haro et al, who used the dehydration rat model 32 . The use of dehydration could potentially have inhibited the latter from also measuring brain volumes; thus, our findings extended their results to show a direct association between brain volume deficits and cellular changes.…”

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.…”

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

“…Earlier post-mortem human studies had suggested fine-grained changes in neuronal morphology (Martin 1958;Neum€ arker et al 1997); however, they did not systematically examine glial cells. In the only study, focussing on glial cell numbers in AN, Reyes-Haro et al (2015) found that the number of GFAP-positive astrocytes in the body of the corpus callosum (not in the splenium and genu) was significantly reduced in acute dehydration-induced anorexia rats but not in a food-restricted only group without dehydration. Furthermore, the astrocyte/glial cell ratio was lower in both starvation groups compared to controls.…”

“…These effects were not prominent in regions with known neurogenesis, such as the subgranular zone of the dentate gyrus, leading the authors of that paper to suspect a primary effect on gliogenesis. Furthermore, Reyes-Haro et al (2015) showed that the astrocyte count was slightly reduced in a different animal model for AN, which is based on acute dehydration, in a subregion of the corpus callosum. However, neither paper combined volumetric and cellular measurements.…”