The demyelinating agent cuprizone induces a male-specific reduction in binge eating in the binge-prone C57BL/6NJ strain

Babbs, R. K.; Beierle, J. A.; Kelliher, J. C.; Medeiros, A. R.; Anandakumar, J.; Shah, A.; Yao, E. J.; Chen, M. M.; Bryant, C. D.

doi:10.1101/865600

bioRxiv · 10.1101/865600

The demyelinating agent cuprizone induces a male-specific reduction in binge eating in the binge-prone C57BL/6NJ strain

Babbs, R. K.·Beierle, J. A.·Kelliher, J. C.·Medeiros, A. R.·Anandakumar, J.·Shah, A.·Yao, E. J.·Chen, M. M.·Bryant, C. D.

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Abstract

Binge eating (BE) is a heritable symptom of eating disorders with an unknown genetic etiology. Rodent models for BE of palatable food permit the study of genetic and biological mechanisms. We previously used genetic mapping and transcriptome analysis to map a coding mutation in Cyfip2 associated with increased BE in the BE-prone C57BL/6NJ substrain compared to the BE-resistant C57BL/6J substrain. The increase in BE in C57BL/6NJ mice was associated with a decrease in transcription of genes enriched for myelination in the striatum. Here, we tested the hypothesis that decreasing myelin levels with the demyelinating agent cuprizone would enhance BE. Mice were treated with a 0.3% cuprizone home cage diet for two weeks. Following a three-week recovery period, mice were trained for BE in an intermittent, limited access procedure. Cuprizone induced similar weight loss in both substrains and sexes that recovered within 48 h after removal of the cuprizone diet. Surprisingly, cuprizone reduced BE in male but not female C57BL/6NJ mice while having no effect in C57BL/6J mice. Cuprizone also reduced myelin basic protein (MBP) at seven weeks post-cuprizone removal while having no effect on myelin-associated glycoprotein (MAG) at this time point. C57BL/6N mice also showed less MBP than C57BL/6J mice. There were no statistical interactions of Treatment with Sex on MBP levels, indicating that differences in MBP are unlikely to account for sex differences in BE. To summarize, cuprizone induced an unexpected, male-specific reduction in BE which could indicate sex-specific biological mechanisms that depend on genetic background.

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Babbs, R. K., Beierle, J. A., Kelliher, J. C., Medeiros, A. R., Anandakumar, J., Shah, A., Yao, E. J., Chen, M. M., Bryant, C. D.. 2019-12-05. The demyelinating agent cuprizone induces a male-specific reduction in binge eating in the binge-prone C57BL/6NJ strain. https://doi.org/10.1101/865600

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