Myelination Deficits in the Auditory Brainstem of a Mouse Model of Fragile X Syndrome.
Myelination Deficits in the Auditory Brainstem of a Mouse Model of Fragile X Syndrome.
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DOI：
10.3389/fnins.2021.772943
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发表时间：
2021
影响因子：
4.3
通讯作者：
McCullagh EA
中科院分区：
文献类型：
--
作者：
Lucas A;Poleg S;Klug A;McCullagh EA
听觉症状是脆性X综合征（FXS）患者最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正在探索中。在这项研究中，我们检查是否有缺陷的髓鞘在听觉脑干回路。具体来说，我们研究了终止于Held的萼的有髓纤维，其编码时间上精确的声音到达时间，并且是大脑中最重的有髓轴突中的一些。我们在FXS小鼠模型中使用相干反斯托克斯拉曼光谱（汽车）和电子显微镜（EM）测量了梯形体内侧核（MNTB）的解剖髓鞘形成特征，其中Hold突触的萼。我们测量了成熟少突胶质细胞（OL）和少突胶质前体细胞（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胶质细胞数量的变化。两种显微镜技术（EM和汽车）显示FXS小鼠的纤维直径减少。此外，EM结果表明髓鞘厚度和轴突直径的减少，以及g-比率的增加，g-比率是结构和功能髓鞘形成的量度。最后，我们显示在FXS小鼠的MNTB切片中OL和OPCs均增加，表明髓鞘形成表型不是由于髓鞘形成OL数量的总体减少。这是第一个研究表明，髓鞘缺陷的听觉脑干，可能是听觉表型的FXS。
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.
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影响因子：
2
作者：
Gundersen, HJG;Jensen, EBV;Nielsen, J
通讯作者：
Nielsen, J
DOI：
10.1073/pnas.0607817104
发表时间：
2007-01-09
影响因子：
11.1
作者：
Bitto, Eduard;Bingman, Craig A.;Phillips, George N., Jr.
通讯作者：
Phillips, George N., Jr.
影响因子：
3.5
作者：
Giampetruzzi, Anthony;Carson, John H.;Barbarese, Elisa
通讯作者：
Barbarese, Elisa
影响因子：
25
作者：
Barak, Boaz;Zhang, Zicong;Feng, Guoping
通讯作者：
Feng, Guoping
影响因子：
5.3
作者：
Curry, Rebecca J.;Peng, Kang;Lu, Yong
通讯作者：
Lu, Yong