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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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.772943/full |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T20:51:37Z |
| format | Article |
| id | doaj.art-12cbf827ba7a41efb41b6e0f7b4f8f25 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-11T20:51:37Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-12cbf827ba7a41efb41b6e0f7b4f8f252022-12-22T04:03:49ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-11-011510.3389/fnins.2021.772943772943Myelination Deficits in the Auditory Brainstem of a Mouse Model of Fragile X SyndromeAlexandra Lucas0Shani Poleg1Achim Klug2Elizabeth A. McCullagh3Department of Physiology and Biophysics, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Physiology and Biophysics, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Physiology and Biophysics, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Integrative Biology, Oklahoma State University, Stillwater, OK, United StatesAuditory 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.https://www.frontiersin.org/articles/10.3389/fnins.2021.772943/fullmyelinationauditory brainstemFragile X Syndromecoherent anti-stokes Raman scatteringmedial nucleus of the trapezoid body |
| spellingShingle | Alexandra Lucas Shani Poleg Achim Klug Elizabeth A. McCullagh Myelination Deficits in the Auditory Brainstem of a Mouse Model of Fragile X Syndrome Frontiers in Neuroscience myelination auditory brainstem Fragile X Syndrome coherent anti-stokes Raman scattering medial nucleus of the trapezoid body |
| 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 | myelination auditory brainstem Fragile X Syndrome coherent anti-stokes Raman scattering medial nucleus of the trapezoid body |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2021.772943/full |
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