Abstract
Anorexia nervosa (AN) is an eating disorder to which adolescent females are particularly vulnerable. Like AN, activity-based anorexia (ABA), a rodent model of AN, results in elevation of stress hormones and has genetic links to anxiety disorders. The hippocampus plays a key role in the regulation of anxiety and responds with structural changes to hormones and stress, suggesting that it may play a role in AN. The hippocampus of ABA animals exhibits increased brain-derived neurotrophic factor and increased GABA receptor expression, but the structural effects of ABA have not been studied. We used Golgi staining of neurons to determine whether ABA in female rats during adolescence results in structural changes to the apical dendrites in hippocampal CA1 and contrasted to the effects of food restriction (FR) and exercise (EX), the environmental factors used to induce ABA. In the dorsal hippocampus, which preferentially mediates spatial learning and cognition, cells of ABA animals had less total dendritic length and fewer dendritic branches in stratum radiatum (SR) than in control (CON). In the ventral hippocampus, which preferentially mediates anxiety, ABA evoked more branching in SR than CON. In both dorsal and ventral regions, the main effect of exercise was localized to the SR while the main effect of food restriction occurred in the stratum lacunosum-moleculare. Taken together with data on spine density, these results indicate that ABA elicits pathway-specific changes in the hippocampus that may underlie the increased anxiety and reduced behavioral flexibility observed in ABA.
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Acknowledgments
This study was supported by the following Grants: The Klarman Foundation Grant Program in Eating Disorders Research, National Institutes for Health Grants R21MH091445-01 to CA and NBM, R01NS066019-01A1 to CA, R01NS047557-07A1 to CA, NEI Core Grant EY13079 to CA, R25GM097634-01 to CA, UL1 TR000038 from the National Center for the Advancement of Translational Science (NCATS) to TGC. We thank Kevin Laurino and Anna Rita Colacino for their help with animal husbandry and behavioral data collection. We thank Nicole Sabaliauskas and Gauri Wable for providing valuable feedback on the analysis and interpretation of results.
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Chowdhury, T.G., Barbarich-Marsteller, N.C., Chan, T.E. et al. Activity-based anorexia has differential effects on apical dendritic branching in dorsal and ventral hippocampal CA1. Brain Struct Funct 219, 1935–1945 (2014). https://doi.org/10.1007/s00429-013-0612-9
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DOI: https://doi.org/10.1007/s00429-013-0612-9