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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: Lucas, Alexandra, Poleg, Shani, Klug, Achim, McCullagh, Elizabeth A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632548/
https://www.ncbi.nlm.nih.gov/pubmed/34858133
http://dx.doi.org/10.3389/fnins.2021.772943
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author Lucas, Alexandra
Poleg, Shani
Klug, Achim
McCullagh, Elizabeth A.
author_facet Lucas, Alexandra
Poleg, Shani
Klug, Achim
McCullagh, Elizabeth A.
author_sort Lucas, Alexandra
collection PubMed
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.
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spelling pubmed-86325482021-12-01 Myelination Deficits in the Auditory Brainstem of a Mouse Model of Fragile X Syndrome Lucas, Alexandra Poleg, Shani Klug, Achim McCullagh, Elizabeth A. Front Neurosci Neuroscience 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. Frontiers Media S.A. 2021-11-11 /pmc/articles/PMC8632548/ /pubmed/34858133 http://dx.doi.org/10.3389/fnins.2021.772943 Text en Copyright © 2021 Lucas, Poleg, Klug and McCullagh. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Lucas, Alexandra
Poleg, Shani
Klug, Achim
McCullagh, Elizabeth A.
Myelination Deficits in the Auditory Brainstem of a Mouse Model of Fragile X Syndrome
title 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_short 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
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632548/
https://www.ncbi.nlm.nih.gov/pubmed/34858133
http://dx.doi.org/10.3389/fnins.2021.772943
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