Fragile X syndrome (FXS) is the most commonly inherited form of intellectual disability ascribed to the autism spectrum disorder. Studies with FXS patients have reported altered white matter volume compared to controls. The Fmr1 knockout (KO) mouse, a model for FXS, showed evidence of delayed myelination during postnatal brain development. In this study, we examined several white matter regions in the male Fmr1 KO mouse brain compared to male wild-type (WT) mice at postnatal days (PND) 18, 21, 30, and 60, which coincide with critical stages of myelination and postnatal brain development. White matter volume, T₂ relaxation time, and magnetization transfer ratio (MTR) were measured using magnetic resonance imaging and myelin content was determined with histological staining of myelin. Differences in the developmental accumulation of white matter and myelin between Fmr1 KO and WT mice were observed in the corpus callosum, external and internal capsules, cerebral peduncle, and fimbria. Alterations were more predominant in the external and internal capsules and fimbria of Fmr1 KO mice, where the MTR was lower at PND 18, then elevated at PND 30, and again lower at PND 60 compared to the corresponding regions in WT mice. The pattern of changes in MTR were similar to those observed in myelin staining and could be related to the altered protein synthesis that is a hallmark of FXS. While no significant changes in white matter volumes and T₂ relaxation time between the Fmr1 KO and WT mice were observed, the altered pattern of myelin staining and MTR, particularly in the external capsule, reflecting the abnormalities associated with myelin content is suggestive of a developmental delay in the white matter of Fmr1 KO mouse brain. These early differences in white matter during critical developmental stages may contribute to altered brain networks in the Fmr1 KO mice.
Dev Neurosci

中文翻译：

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产后早期大脑发育过程中Fmr1基因敲除小鼠的白色物质变化。

易碎X综合征（FXS）是归因于自闭症谱系障碍的智力障碍的最常见遗传形式。FXS患者的研究报告了与对照组相比，白质量改变了。在Fmr1基因敲除（KO）鼠标，用于FXS模型，出生后大脑发育过程中的髓鞘延迟显示的证据。在这项研究中，我们检查了在出生后第18、21、30和60天，与雄性野生型（WT）小鼠相比，雄性Fmr1 KO小鼠大脑中的几个白质区域，这与髓鞘形成的关键时期和产后大脑发育。白质体积，T ₂使用磁共振成像测量弛豫时间和磁化传递比（MTR），并通过髓磷脂的组织学染色确定髓磷脂含量。Fmr1 KO和WT小鼠之间的白质和髓鞘的发育积累差异在cerebral体，内外囊，内囊，脑柄和菌毛中观察到。Fmr1的内，外囊和纤维膜的改变更为明显与WT小鼠的相应区域相比，KO小鼠的MTR在PND 18较低，然后在PND 30升高，然后在PND 60较低。MTR的变化模式与髓磷脂染色中观察到的模式相似，并且可能与蛋白质合成的改变有关，这是FXS的标志。虽然在Fmr1 KO和WT小鼠之间未观察到白质体积和T ₂弛豫时间的显着变化，但髓磷脂染色和MTR的改变模式，特别是在外囊中，反映了与髓磷脂含量相关的异常提示发育延缓Fmr1的白质KO老鼠的大脑。在关键的发育阶段，白质的这些早期差异可能导致Fmr1 KO小鼠大脑网络的改变。
开发神经科学