Myelination Deficits in the Auditory Brainstem of a Mouse Model of Fragile X Syndrome

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 my...

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Autores principales:	Alexandra Lucas, Shani Poleg, Achim Klug, Elizabeth A. McCullagh
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	myelination auditory brainstem Fragile X Syndrome coherent anti-stokes Raman scattering medial nucleus of the trapezoid body Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/12cbf827ba7a41efb41b6e0f7b4f8f25
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spelling	oai:doaj.org-article:12cbf827ba7a41efb41b6e0f7b4f8f252021-11-11T10:24:33ZMyelination Deficits in the Auditory Brainstem of a Mouse Model of Fragile X Syndrome1662-453X10.3389/fnins.2021.772943https://doaj.org/article/12cbf827ba7a41efb41b6e0f7b4f8f252021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnins.2021.772943/fullhttps://doaj.org/toc/1662-453XAuditory 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.Alexandra LucasShani PolegAchim KlugElizabeth A. McCullaghFrontiers Media S.A.articlemyelinationauditory brainstemFragile X Syndromecoherent anti-stokes Raman scatteringmedial nucleus of the trapezoid bodyNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	myelination auditory brainstem Fragile X Syndrome coherent anti-stokes Raman scattering medial nucleus of the trapezoid body Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	myelination auditory brainstem Fragile X Syndrome coherent anti-stokes Raman scattering medial nucleus of the trapezoid body Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Alexandra Lucas Shani Poleg Achim Klug Elizabeth A. McCullagh Myelination Deficits in the Auditory Brainstem of a Mouse Model of Fragile X Syndrome
description	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.
format	article
author	Alexandra Lucas Shani Poleg Achim Klug Elizabeth A. McCullagh
author_facet	Alexandra Lucas Shani Poleg Achim Klug Elizabeth A. McCullagh
author_sort	Alexandra Lucas
title	Myelination Deficits in the Auditory Brainstem of a Mouse Model of Fragile X Syndrome
title_short	Myelination Deficits in the Auditory Brainstem of a Mouse Model of Fragile X Syndrome
title_full	Myelination Deficits in the Auditory Brainstem of a Mouse Model of Fragile X Syndrome
title_fullStr	Myelination Deficits in the Auditory Brainstem of a Mouse Model of Fragile X Syndrome
title_full_unstemmed	Myelination Deficits in the Auditory Brainstem of a Mouse Model of Fragile X Syndrome
title_sort	myelination deficits in the auditory brainstem of a mouse model of fragile x syndrome
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/12cbf827ba7a41efb41b6e0f7b4f8f25
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_version_	1718439102807801856

Myelination Deficits in the Auditory Brainstem of a Mouse Model of Fragile X Syndrome

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