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

Richard K. Babbs; Jacob A. Beierle; Julia C. Kelliher; Rose Medeiros; Jeya Anandakumar; Anyaa Shah; Emily J. Yao; Melanie M. Chen; Camron D. Bryant

Binge eating (BE) is operationally defined as the consumption of a relatively large amount 54 of food over a short period of time, and is accompanied by feelings of loss of control (Amianto, 55 Ottone, Abbate Daga, & Fassino, 2015) . Repeated BE that occurs at least once per week for at 56 least three months is termed binge eating disorder (BED). BE has a lifetime prevalence of 57 approximately 4.5% (Hudson, Hiripi, Pope, & Kessler, 2007) and is associated with a number of 58 comorbid behavioral, mood, and physical disorders such as substance abuse, depression, 59 obesity, and chronic pain (Bulik & Reichborn-Kjennerud, 2003; Citrome, 2017; Hudson et al., 60 2007) . Although there is no sex difference in the lifetime prevalence of BE, women are nearly 61 twice as likely as men to progress to the more severe BED (3.5% vs. 2.0% respectively (Hudson 62 et al., 2007) . However, the etiology of this sex difference is not known. amygdala-hippocampus complex in AN, and greater frontal cortical response to food stimuli in 69 BED (Geliebter et al., 2006) . Another important neuroanatomical change common to multiple 70 types of ED involves changes in myelin which is the lipid-rich, membranous insulation sheath that 71 extends from oligodendrocytes to the axons and is involved in axon maintenance (via 72 oligodendrocyte signaling) and function, including rapid salutatory conduction of action potentials. 73 BN is associated with a reduction in fractional anisotropy, a brain imaging measure of white matter 74 integrity, in the corona radiata and corpus callosum ( For MAG detection, blots were incubated in a 1:5,000 dilution of anti-MAG antibody (EMD 194 Millipore, Burlington, MA, USA, #MAB1567) in 5% BSA in TBST overnight at 4C, then a 1:10,000 195 dilution of peroxidase conjugated donkey anti mouse antibody (Jackson Immunoresearch, West 196