Structural and molecular myelination deficits represent early pathological features of Huntington disease (HD). Recent evidence from germ-free (GF) animals suggests a role for microbiota-gut-brain bidirectional communication in the regulation of myelination. In this study, we aimed to investigate the impact of microbiota on myelin plasticity and oligodendroglial population dynamics in the mixed-sex BACHD mouse model of HD. Ultrastructural analysis of myelin in the corpus callosum revealed alterations of myelin thickness in BACHD GF compared to specific-pathogen free (SPF) mice, whereas no differences were observed between wild-type (WT) groups. In contrast, myelin compaction was altered in all groups when compared to WT SPF animals. Levels of myelin-related proteins were generally reduced, and the number of mature oligodendrocytes was decreased in the prefrontal cortex under GF compared to SPF conditions, regardless of genotype. Minor differences in commensal bacteria at the family and genera levels were found in the gut microbiota of BACHD and WT animals housed in standard living conditions. Our findings indicate complex effects of a germ-free status on myelin-related characteristics, and highlight the adaptive properties of myelination as a result of environmental manipulation.

中文翻译：

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转载：微生物群的操纵揭示了亨廷顿病模型中call的髓鞘化和白质可塑性改变。

结构和分子髓鞘缺乏症代表了亨廷顿舞蹈病（HD）的早期病理特征。来自无菌（GF）动物的最新证据表明，微生物-肠-脑双向通讯在调节髓鞘形成中起作用。在这项研究中，我们旨在研究微生物群对HD混合性BACHD小鼠模型中髓鞘可塑性和少突胶质细胞种群动态的影响。call体中髓磷脂的超微结构分析显示，与无特定病原体（SPF）的小鼠相比，BACHD GF中髓磷脂的厚度发生了变化，而野生型（WT）组之间没有发现差异。相反，与WT SPF动物相比，所有组的髓磷脂压实度均发生变化。髓磷脂相关蛋白的水平通常会降低，与SPF条件相比，GF基因组在前额叶皮层中成熟少突胶质细胞的数量减少，而与基因型无关。在正常生活条件下饲养的BACHD和WT动物的肠道菌群中，在科和属水平上的共生细菌存在微小差异。我们的发现表明，无菌状态对髓鞘相关特征的复杂影响，并突出了环境操作导致的髓鞘适应性。