Binge eating (BE) is a heritable symptom of eating disorders with an unknown genetic etiology. Rodent models for binge-like eating (BLE) of palatable food permit the study of genetic and biological mechanisms. We previously genetically mapped a coding mutation in Cyfip2 associated with increased BLE of sweetened palatable food in the C57BL/6NJ versus C57BL/6J substrain. The increase in BLE 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 BLE. Mice were treated with a 0.3% cuprizone home cage diet for two weeks. Cuprizone induced similar weight loss in both substrains and sexes that recovered within 48 h after removal of cuprizone. Following a three-week recovery period, mice were trained for BLE in an intermittent, limited access procedure. Surprisingly, cuprizone significantly reduced BLE 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 at this time point. C57BL/6NJ 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 reduction are unlikely to account for sex differences in BLE. To summarize, cuprizone induced an unexpected, significant reduction in BLE in B6NJ males which could indicate genotype-dependent sex differences in the biological mechanisms of BLE.

中文翻译：

---

脱髓鞘剂铜宗对雌性和雄性C57BL/6亚株甜食暴食的影响

暴饮暴食 (BE) 是遗传病因不明的饮食失调症的遗传症状。用于可口食物的类似暴饮暴食 (BLE) 的啮齿动物模型允许研究遗传和生物机制。我们之前对 Cyfip2 中的一个编码突变进行了基因定位，该突变与 C57BL/6NJ 与 C57BL/6J 亚株中加糖可口食物的 BLE 增加有关。C57BL/6NJ 小鼠 BLE 的增加与纹状体中富含髓鞘的基因转录减少有关。在这里，我们测试了使用脱髓鞘剂铜宗降低髓鞘水平会增强 BLE 的假设。小鼠用 0.3% 铜宗笼养笼饮食治疗两周。Cuprizone 在去除铜宗后 48 小时内在亚种和性别中引起相似的体重减轻。经过三周的恢复期，在间歇性、有限访问程序中对小鼠进行 BLE 训练。令人惊讶的是，铜宗显着降低了雄性而非雌性 C57BL/6NJ 小鼠的 BLE，而对 C57BL/6J 小鼠没有影响。Cuprizone 在去除铜宗后 7 周还降低了髓鞘碱性蛋白 (MBP)，而此时对髓磷脂相关糖蛋白没有影响。C57BL/6NJ 小鼠的 MBP 也低于 C57BL/6J 小鼠。性别治疗对 MBP 水平没有统计交互作用，表明 MBP 降低的差异不太可能解释 BLE 的性别差异。总而言之，铜宗导致 B6NJ 雄性 BLE 意外显着降低，这可能表明 BLE 生物学机制中的基因型依赖性性别差异。令人惊讶的是，铜宗显着降低了雄性而非雌性 C57BL/6NJ 小鼠的 BLE，而对 C57BL/6J 小鼠没有影响。Cuprizone 在去除铜宗后 7 周还降低了髓鞘碱性蛋白 (MBP)，而此时对髓磷脂相关糖蛋白没有影响。C57BL/6NJ 小鼠的 MBP 也低于 C57BL/6J 小鼠。性别治疗对 MBP 水平没有统计交互作用，表明 MBP 降低的差异不太可能解释 BLE 的性别差异。总而言之，铜宗导致 B6NJ 雄性 BLE 意外显着降低，这可能表明 BLE 生物学机制中的基因型依赖性性别差异。令人惊讶的是，铜宗显着降低了雄性而非雌性 C57BL/6NJ 小鼠的 BLE，而对 C57BL/6J 小鼠没有影响。Cuprizone 在去除铜宗后 7 周还降低了髓鞘碱性蛋白 (MBP)，而此时对髓磷脂相关糖蛋白没有影响。C57BL/6NJ 小鼠的 MBP 也低于 C57BL/6J 小鼠。性别治疗对 MBP 水平没有统计交互作用，表明 MBP 降低的差异不太可能解释 BLE 的性别差异。总而言之，铜宗导致 B6NJ 雄性 BLE 意外显着降低，这可能表明 BLE 生物学机制中的基因型依赖性性别差异。Cuprizone 在去除铜宗后 7 周还降低了髓鞘碱性蛋白 (MBP)，而此时对髓磷脂相关糖蛋白没有影响。C57BL/6NJ 小鼠的 MBP 也低于 C57BL/6J 小鼠。性别治疗对 MBP 水平没有统计交互作用，表明 MBP 降低的差异不太可能解释 BLE 的性别差异。总而言之，铜宗导致 B6NJ 雄性 BLE 意外显着降低，这可能表明 BLE 生物学机制中的基因型依赖性性别差异。Cuprizone 在去除铜宗后 7 周还降低了髓鞘碱性蛋白 (MBP)，而此时对髓磷脂相关糖蛋白没有影响。C57BL/6NJ 小鼠的 MBP 也低于 C57BL/6J 小鼠。性别治疗对 MBP 水平没有统计交互作用，表明 MBP 降低的差异不太可能解释 BLE 的性别差异。总而言之，铜宗导致 B6NJ 雄性 BLE 意外显着降低，这可能表明 BLE 生物学机制中的基因型依赖性性别差异。表明 MBP 降低的差异不太可能解释 BLE 的性别差异。总而言之，铜宗导致 B6NJ 雄性 BLE 意外显着降低，这可能表明 BLE 生物学机制中的基因型依赖性性别差异。表明 MBP 降低的差异不太可能解释 BLE 的性别差异。总而言之，铜宗导致 B6NJ 雄性 BLE 意外显着降低，这可能表明 BLE 生物学机制中的基因型依赖性性别差异。