Neuroprotective Effect of Glatiramer Acetate on Neurofilament Light Chain Leakage and Glutamate Excess in an Animal Model of Multiple Sclerosis
Axonal and neuronal pathologies are a central constituent of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), induced by the myelin oligodendrocyte glycoprotein (MOG) 35–55 peptide. In this study, we investigated neurodegenerative manifestations in chron...
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/24/13419 |
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| author | Rina Aharoni Raya Eilam Shaul Lerner Efrat Shavit-Stein Amir Dori Joab Chapman Ruth Arnon |
| author_facet | Rina Aharoni Raya Eilam Shaul Lerner Efrat Shavit-Stein Amir Dori Joab Chapman Ruth Arnon |
| author_sort | Rina Aharoni |
| collection | DOAJ |
| description | Axonal and neuronal pathologies are a central constituent of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), induced by the myelin oligodendrocyte glycoprotein (MOG) 35–55 peptide. In this study, we investigated neurodegenerative manifestations in chronic MOG 35–55 induced EAE and the effect of glatiramer acetate (GA) treatment on these manifestations. We report that the neuronal loss seen in this model is not attributed to apoptotic neuronal cell death. In EAE-affected mice, axonal damage prevails from the early disease phase, as revealed by analysis of neurofilament light (NFL) leakage into the sera along the disease duration, as well as by immunohistological examination. Elevation of interstitial glutamate concentrations measured in the cerebrospinal fluid (CSF) implies that glutamate excess plays a role in the damage processes inflicted by this disease. GA applied as a therapeutic regimen to mice with apparent clinical symptoms significantly reduces the pathological manifestations, namely apoptotic cell death, NFL leakage, histological tissue damage, and glutamate excess, thus corroborating the neuroprotective consequences of this treatment. |
| first_indexed | 2024-03-10T03:55:46Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:55:46Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a02eb4baca554e88871e90e91370be8d2023-11-23T08:46:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241341910.3390/ijms222413419Neuroprotective Effect of Glatiramer Acetate on Neurofilament Light Chain Leakage and Glutamate Excess in an Animal Model of Multiple SclerosisRina Aharoni0Raya Eilam1Shaul Lerner2Efrat Shavit-Stein3Amir Dori4Joab Chapman5Ruth Arnon6Department of Immunology, The Weizmann Institute of Science, Rehovot 761001, IsraelDepartment of Brain Sciences, The Weizmann Institute of Science, Rehovot 761001, IsraelDepartment of Biological Regulation, The Weizmann Institute of Science, Rehovot 761001, IsraelDepartment of Neurology, Sheba Medical Center, Ramat Gan 5262000, IsraelDepartment of Neurology, Sheba Medical Center, Ramat Gan 5262000, IsraelDepartment of Neurology, Sheba Medical Center, Ramat Gan 5262000, IsraelDepartment of Immunology, The Weizmann Institute of Science, Rehovot 761001, IsraelAxonal and neuronal pathologies are a central constituent of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), induced by the myelin oligodendrocyte glycoprotein (MOG) 35–55 peptide. In this study, we investigated neurodegenerative manifestations in chronic MOG 35–55 induced EAE and the effect of glatiramer acetate (GA) treatment on these manifestations. We report that the neuronal loss seen in this model is not attributed to apoptotic neuronal cell death. In EAE-affected mice, axonal damage prevails from the early disease phase, as revealed by analysis of neurofilament light (NFL) leakage into the sera along the disease duration, as well as by immunohistological examination. Elevation of interstitial glutamate concentrations measured in the cerebrospinal fluid (CSF) implies that glutamate excess plays a role in the damage processes inflicted by this disease. GA applied as a therapeutic regimen to mice with apparent clinical symptoms significantly reduces the pathological manifestations, namely apoptotic cell death, NFL leakage, histological tissue damage, and glutamate excess, thus corroborating the neuroprotective consequences of this treatment.https://www.mdpi.com/1422-0067/22/24/13419multiple sclerosis (MS)experimental autoimmune encephalomyelitis (EAE)glatiramer acetate (GA)neurodegenerationneurofilament light (NFL)glutamate |
| spellingShingle | Rina Aharoni Raya Eilam Shaul Lerner Efrat Shavit-Stein Amir Dori Joab Chapman Ruth Arnon Neuroprotective Effect of Glatiramer Acetate on Neurofilament Light Chain Leakage and Glutamate Excess in an Animal Model of Multiple Sclerosis International Journal of Molecular Sciences multiple sclerosis (MS) experimental autoimmune encephalomyelitis (EAE) glatiramer acetate (GA) neurodegeneration neurofilament light (NFL) glutamate |
| title | Neuroprotective Effect of Glatiramer Acetate on Neurofilament Light Chain Leakage and Glutamate Excess in an Animal Model of Multiple Sclerosis |
| title_full | Neuroprotective Effect of Glatiramer Acetate on Neurofilament Light Chain Leakage and Glutamate Excess in an Animal Model of Multiple Sclerosis |
| title_fullStr | Neuroprotective Effect of Glatiramer Acetate on Neurofilament Light Chain Leakage and Glutamate Excess in an Animal Model of Multiple Sclerosis |
| title_full_unstemmed | Neuroprotective Effect of Glatiramer Acetate on Neurofilament Light Chain Leakage and Glutamate Excess in an Animal Model of Multiple Sclerosis |
| title_short | Neuroprotective Effect of Glatiramer Acetate on Neurofilament Light Chain Leakage and Glutamate Excess in an Animal Model of Multiple Sclerosis |
| title_sort | neuroprotective effect of glatiramer acetate on neurofilament light chain leakage and glutamate excess in an animal model of multiple sclerosis |
| topic | multiple sclerosis (MS) experimental autoimmune encephalomyelitis (EAE) glatiramer acetate (GA) neurodegeneration neurofilament light (NFL) glutamate |
| url | https://www.mdpi.com/1422-0067/22/24/13419 |
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