Aquaporin-4 Expression during Toxic and Autoimmune Demyelination
The water channel protein aquaporin-4 (AQP4) is required for a normal rate of water exchange across the blood–brain interface. Following the discovery that AQP4 is a possible autoantigen in neuromyelitis optica, the function of AQP4 in health and disease has become a research focus. While several st...
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MDPI AG
2020-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/10/2187 |
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| author | Sven Olaf Rohr Theresa Greiner Sarah Joost Sandra Amor Paul van der Valk Christoph Schmitz Markus Kipp |
| author_facet | Sven Olaf Rohr Theresa Greiner Sarah Joost Sandra Amor Paul van der Valk Christoph Schmitz Markus Kipp |
| author_sort | Sven Olaf Rohr |
| collection | DOAJ |
| description | The water channel protein aquaporin-4 (AQP4) is required for a normal rate of water exchange across the blood–brain interface. Following the discovery that AQP4 is a possible autoantigen in neuromyelitis optica, the function of AQP4 in health and disease has become a research focus. While several studies have addressed the expression and function of AQP4 during inflammatory demyelination, relatively little is known about its expression during non-autoimmune-mediated myelin damage. In this study, we used the toxin-induced demyelination model cuprizone as well as a combination of metabolic and autoimmune myelin injury (i.e., Cup/EAE) to investigate AQP4 pathology. We show that during toxin-induced demyelination, diffuse AQP4 expression increases, while polarized AQP4 expression at the astrocyte endfeet decreases. The diffuse increased expression of AQP4 was verified in chronic-active multiple sclerosis lesions. Around inflammatory brain lesions, AQP4 expression dramatically decreased, especially at sites where peripheral immune cells penetrate the brain parenchyma. Humoral immune responses appear not to be involved in this process since no anti-AQP4 antibodies were detected in the serum of the experimental mice. We provide strong evidence that the diffuse increase in anti-AQP4 staining intensity is due to a metabolic injury to the brain, whereas the focal, perivascular loss of anti-AQP4 immunoreactivity is mediated by peripheral immune cells. |
| first_indexed | 2024-03-10T15:58:52Z |
| format | Article |
| id | doaj.art-74f3a7c57c4b4c5fa84523ac53bd50de |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T15:58:52Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-74f3a7c57c4b4c5fa84523ac53bd50de2023-11-20T15:25:40ZengMDPI AGCells2073-44092020-09-01910218710.3390/cells9102187Aquaporin-4 Expression during Toxic and Autoimmune DemyelinationSven Olaf Rohr0Theresa Greiner1Sarah Joost2Sandra Amor3Paul van der Valk4Christoph Schmitz5Markus Kipp6Institute of Anatomy, Rostock University Medical Center, Gertrudenstrasse 9, 18057 Rostock, GermanyInstitute of Anatomy, Rostock University Medical Center, Gertrudenstrasse 9, 18057 Rostock, GermanyInstitute of Anatomy, Rostock University Medical Center, Gertrudenstrasse 9, 18057 Rostock, GermanyDepartment of Pathology, VU Medical Center, De Boelelaan 1117, ZH 3E36 1081 HV Amsterdam, The NetherlandsDepartment of Pathology, VU Medical Center, De Boelelaan 1117, ZH 3E36 1081 HV Amsterdam, The NetherlandsInstitute of Anatomy II, Faculty of Medicine, LMU Munich, Pettenkoferstrasse 11, 80336 Munich, GermanyInstitute of Anatomy, Rostock University Medical Center, Gertrudenstrasse 9, 18057 Rostock, GermanyThe water channel protein aquaporin-4 (AQP4) is required for a normal rate of water exchange across the blood–brain interface. Following the discovery that AQP4 is a possible autoantigen in neuromyelitis optica, the function of AQP4 in health and disease has become a research focus. While several studies have addressed the expression and function of AQP4 during inflammatory demyelination, relatively little is known about its expression during non-autoimmune-mediated myelin damage. In this study, we used the toxin-induced demyelination model cuprizone as well as a combination of metabolic and autoimmune myelin injury (i.e., Cup/EAE) to investigate AQP4 pathology. We show that during toxin-induced demyelination, diffuse AQP4 expression increases, while polarized AQP4 expression at the astrocyte endfeet decreases. The diffuse increased expression of AQP4 was verified in chronic-active multiple sclerosis lesions. Around inflammatory brain lesions, AQP4 expression dramatically decreased, especially at sites where peripheral immune cells penetrate the brain parenchyma. Humoral immune responses appear not to be involved in this process since no anti-AQP4 antibodies were detected in the serum of the experimental mice. We provide strong evidence that the diffuse increase in anti-AQP4 staining intensity is due to a metabolic injury to the brain, whereas the focal, perivascular loss of anti-AQP4 immunoreactivity is mediated by peripheral immune cells.https://www.mdpi.com/2073-4409/9/10/2187aquaporin 4cuprizoneexperimental autoimmune encephalomyelitisdemyelinationblood–brain barriermultiple sclerosis |
| spellingShingle | Sven Olaf Rohr Theresa Greiner Sarah Joost Sandra Amor Paul van der Valk Christoph Schmitz Markus Kipp Aquaporin-4 Expression during Toxic and Autoimmune Demyelination Cells aquaporin 4 cuprizone experimental autoimmune encephalomyelitis demyelination blood–brain barrier multiple sclerosis |
| title | Aquaporin-4 Expression during Toxic and Autoimmune Demyelination |
| title_full | Aquaporin-4 Expression during Toxic and Autoimmune Demyelination |
| title_fullStr | Aquaporin-4 Expression during Toxic and Autoimmune Demyelination |
| title_full_unstemmed | Aquaporin-4 Expression during Toxic and Autoimmune Demyelination |
| title_short | Aquaporin-4 Expression during Toxic and Autoimmune Demyelination |
| title_sort | aquaporin 4 expression during toxic and autoimmune demyelination |
| topic | aquaporin 4 cuprizone experimental autoimmune encephalomyelitis demyelination blood–brain barrier multiple sclerosis |
| url | https://www.mdpi.com/2073-4409/9/10/2187 |
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