Lucas Alexandra, Poleg Shani, Klug Achim, McCullagh Elizabeth A
Department of Physiology and Biophysics, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Department of Integrative Biology, Oklahoma State University, Stillwater, OK, United States.
Front Neurosci. 2021 Nov 11;15:772943. doi: 10.3389/fnins.2021.772943. eCollection 2021.
Auditory symptoms are one of the most frequent sensory issues described in people with Fragile X Syndrome (FXS), the most common genetic form of intellectual disability. However, the mechanisms that lead to these symptoms are under explored. In this study, we examined whether there are defects in myelination in the auditory brainstem circuitry. Specifically, we studied myelinated fibers that terminate in the Calyx of Held, which encode temporally precise sound arrival time, and are some of the most heavily myelinated axons in the brain. We measured anatomical myelination characteristics using coherent anti-stokes Raman spectroscopy (CARS) and electron microscopy (EM) in a FXS mouse model in the medial nucleus of the trapezoid body (MNTB) where the Calyx of Held synapses. We measured number of mature oligodendrocytes (OL) and oligodendrocyte precursor cells (OPCs) to determine if changes in myelination were due to changes in the number of myelinating or immature glial cells. The two microscopy techniques (EM and CARS) showed a decrease in fiber diameter in FXS mice. Additionally, EM results indicated reductions in myelin thickness and axon diameter, and an increase in g-ratio, a measure of structural and functional myelination. Lastly, we showed an increase in both OL and OPCs in MNTB sections of FXS mice suggesting that the myelination phenotype is not due to an overall decrease in number of myelinating OLs. This is the first study to show that a myelination defects in the auditory brainstem that may underly auditory phenotypes in FXS.
听觉症状是脆性X综合征（FXS）患者中描述最为常见的感觉问题之一，FXS是智力残疾最常见的遗传形式。然而，导致这些症状的机制尚待探索。在本研究中，我们检查了听觉脑干回路中是否存在髓鞘形成缺陷。具体而言，我们研究了终止于 Held 壶腹的有髓纤维，这些纤维编码时间精确的声音到达时间，并且是大脑中髓鞘最厚的轴突之一。我们在Held壶腹突触所在的梯形体内侧核（MNTB）的FXS小鼠模型中，使用相干反斯托克斯拉曼光谱（CARS）和电子显微镜（EM）测量了解剖学上的髓鞘形成特征。我们测量了成熟少突胶质细胞（OL）和少突胶质细胞前体细胞（OPC）的数量，以确定髓鞘形成的变化是否是由于髓鞘形成或未成熟神经胶质细胞数量的变化。两种显微镜技术（EM和CARS）均显示FXS小鼠的纤维直径减小。此外，EM结果表明髓鞘厚度和轴突直径减小，而g值增加，g值是结构和功能性髓鞘形成的一个指标。最后，我们发现FXS小鼠MNTB切片中的OL和OPC均增加，这表明髓鞘形成表型并非由于髓鞘形成OL的数量总体减少所致。这是第一项表明听觉脑干中的髓鞘形成缺陷可能是FXS听觉表型基础的研究。
