{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:26:25Z","timestamp":1791599185696,"version":"4.3.4"},"reference-count":73,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T00:00:00Z","timestamp":1601251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014276","name":"Dr. Robert Pfleger Stiftung","doi-asserted-by":"publisher","award":["none"],"award-info":[{"award-number":["none"]}],"id":[{"id":"10.13039\/501100014276","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The water channel protein aquaporin-4 (AQP4) is required for a normal rate of water exchange across the blood\u2013brain 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.<\/jats:p>","DOI":"10.3390\/cells9102187","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T10:39:58Z","timestamp":1601289598000},"page":"2187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Aquaporin-4 Expression during Toxic and Autoimmune Demyelination"],"prefix":"10.3390","volume":"9","author":[{"given":"Sven Olaf","family":"Rohr","sequence":"first","affiliation":[{"name":"Institute of Anatomy, Rostock University Medical Center, Gertrudenstrasse 9, 18057 Rostock, Germany"},{"name":"Institute of Anatomy II, Faculty of Medicine, LMU Munich, Pettenkoferstrasse 11, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Greiner","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Rostock University Medical Center, Gertrudenstrasse 9, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8654-8904","authenticated-orcid":false,"given":"Sarah","family":"Joost","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Rostock University Medical Center, Gertrudenstrasse 9, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Amor","sequence":"additional","affiliation":[{"name":"Department of Pathology, VU Medical Center, De Boelelaan 1117, ZH 3E36 1081 HV Amsterdam, The Netherlands"},{"name":"Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark St., London E1 2AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul van der","family":"Valk","sequence":"additional","affiliation":[{"name":"Department of Pathology, VU Medical Center, De Boelelaan 1117, ZH 3E36 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Institute of Anatomy II, Faculty of Medicine, LMU Munich, Pettenkoferstrasse 11, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5043-9052","authenticated-orcid":false,"given":"Markus","family":"Kipp","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Rostock University Medical Center, Gertrudenstrasse 9, 18057 Rostock, Germany"},{"name":"Center for Transdisciplinary Neurosciences Rostock (CTNR), Rostock University Medical Center, Gelsheimer Strasse 20, 18147 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,28]]},"reference":[{"key":"ref_1","first-page":"901","article-title":"Pathology of multiple sclerosis: Where do we stand?","volume":"19","author":"Popescu","year":"2013","journal-title":"Continuum Minneap Minn"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/bpa.12454","article-title":"Multiple sclerosis animal models: A clinical and histopathological perspective","volume":"27","author":"Kipp","year":"2017","journal-title":"Brain Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/S0140-6736(02)08220-X","article-title":"Multiple sclerosis","volume":"359","author":"Compston","year":"2002","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/s41586-020-1999-0","article-title":"MAFG-driven astrocytes promote CNS inflammation","volume":"578","author":"Wheeler","year":"2020","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s11064-020-02968-6","article-title":"Reactive astrocytes as therapeutic targets for brain degenerative diseases: Roles played by metabotropic glutamate receptors","volume":"45","author":"Dreyfus","year":"2020","journal-title":"Neurochem. 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