Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function?
Despite significant advances in our understanding of the pathophysiology of multiple sclerosis (MS), knowledge about contribution of individual ion channels to axonal impairment and remyelination failure in progressive MS remains incomplete. Ion channel families play a fundamental role in maintainin...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2021.685703/full |
| _version_ | 1818576174066958336 |
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| author | Francesca Boscia Maria Louise Elkjaer Maria Louise Elkjaer Zsolt Illes Zsolt Illes Zsolt Illes Maria Kukley Maria Kukley |
| author_facet | Francesca Boscia Maria Louise Elkjaer Maria Louise Elkjaer Zsolt Illes Zsolt Illes Zsolt Illes Maria Kukley Maria Kukley |
| author_sort | Francesca Boscia |
| collection | DOAJ |
| description | Despite significant advances in our understanding of the pathophysiology of multiple sclerosis (MS), knowledge about contribution of individual ion channels to axonal impairment and remyelination failure in progressive MS remains incomplete. Ion channel families play a fundamental role in maintaining white matter (WM) integrity and in regulating WM activities in axons, interstitial neurons, glia, and vascular cells. Recently, transcriptomic studies have considerably increased insight into the gene expression changes that occur in diverse WM lesions and the gene expression fingerprint of specific WM cells associated with secondary progressive MS. Here, we review the ion channel genes encoding K+, Ca2+, Na+, and Cl− channels; ryanodine receptors; TRP channels; and others that are significantly and uniquely dysregulated in active, chronic active, inactive, remyelinating WM lesions, and normal-appearing WM of secondary progressive MS brain, based on recently published bulk and single-nuclei RNA-sequencing datasets. We discuss the current state of knowledge about the corresponding ion channels and their implication in the MS brain or in experimental models of MS. This comprehensive review suggests that the intense upregulation of voltage-gated Na+ channel genes in WM lesions with ongoing tissue damage may reflect the imbalance of Na+ homeostasis that is observed in progressive MS brain, while the upregulation of a large number of voltage-gated K+ channel genes may be linked to a protective response to limit neuronal excitability. In addition, the altered chloride homeostasis, revealed by the significant downregulation of voltage-gated Cl− channels in MS lesions, may contribute to an altered inhibitory neurotransmission and increased excitability. |
| first_indexed | 2024-12-16T06:09:49Z |
| format | Article |
| id | doaj.art-3736944027f948c1b6958b9fb2d2cd2a |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-16T06:09:49Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-3736944027f948c1b6958b9fb2d2cd2a2022-12-21T22:41:25ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022021-06-011510.3389/fncel.2021.685703685703Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function?Francesca Boscia0Maria Louise Elkjaer1Maria Louise Elkjaer2Zsolt Illes3Zsolt Illes4Zsolt Illes5Maria Kukley6Maria Kukley7Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine, University of Naples “Federico II”, Naples, ItalyNeurology Research Unit, Department of Clinical Research, University of Southern Denmark, Odense, DenmarkDepartment of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, DenmarkNeurology Research Unit, Department of Clinical Research, University of Southern Denmark, Odense, DenmarkDepartment of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, DenmarkDepartment of Neurology, Odense University Hospital, Odense, DenmarkAchucarro Basque Center for Neuroscience, Leioa, SpainIkerbasque Basque Foundation for Science, Bilbao, SpainDespite significant advances in our understanding of the pathophysiology of multiple sclerosis (MS), knowledge about contribution of individual ion channels to axonal impairment and remyelination failure in progressive MS remains incomplete. Ion channel families play a fundamental role in maintaining white matter (WM) integrity and in regulating WM activities in axons, interstitial neurons, glia, and vascular cells. Recently, transcriptomic studies have considerably increased insight into the gene expression changes that occur in diverse WM lesions and the gene expression fingerprint of specific WM cells associated with secondary progressive MS. Here, we review the ion channel genes encoding K+, Ca2+, Na+, and Cl− channels; ryanodine receptors; TRP channels; and others that are significantly and uniquely dysregulated in active, chronic active, inactive, remyelinating WM lesions, and normal-appearing WM of secondary progressive MS brain, based on recently published bulk and single-nuclei RNA-sequencing datasets. We discuss the current state of knowledge about the corresponding ion channels and their implication in the MS brain or in experimental models of MS. This comprehensive review suggests that the intense upregulation of voltage-gated Na+ channel genes in WM lesions with ongoing tissue damage may reflect the imbalance of Na+ homeostasis that is observed in progressive MS brain, while the upregulation of a large number of voltage-gated K+ channel genes may be linked to a protective response to limit neuronal excitability. In addition, the altered chloride homeostasis, revealed by the significant downregulation of voltage-gated Cl− channels in MS lesions, may contribute to an altered inhibitory neurotransmission and increased excitability.https://www.frontiersin.org/articles/10.3389/fncel.2021.685703/fullmultiple sclerosisprogressivewhite matterlesionsion channelstranscriptome |
| spellingShingle | Francesca Boscia Maria Louise Elkjaer Maria Louise Elkjaer Zsolt Illes Zsolt Illes Zsolt Illes Maria Kukley Maria Kukley Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function? Frontiers in Cellular Neuroscience multiple sclerosis progressive white matter lesions ion channels transcriptome |
| title | Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function? |
| title_full | Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function? |
| title_fullStr | Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function? |
| title_full_unstemmed | Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function? |
| title_short | Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function? |
| title_sort | altered expression of ion channels in white matter lesions of progressive multiple sclerosis what do we know about their function |
| topic | multiple sclerosis progressive white matter lesions ion channels transcriptome |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2021.685703/full |
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