{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T08:59:47Z","timestamp":1780045187225,"version":"3.53.1"},"reference-count":76,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T00:00:00Z","timestamp":1604534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Olav Thon Foundation-Nordic Research in Medicine","award":["Olav Thon Foundation- 2017"],"award-info":[{"award-number":["Olav Thon Foundation- 2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Aquaporin-4 (AQP4) is critically involved in brain water and volume homeostasis and has been implicated in a wide range of pathological conditions. Notably, evidence has been accrued to suggest that AQP4 plays a proinflammatory role by promoting release of astrocytic cytokines that activate microglia and other astrocytes. Neuroinflammation is a hallmark of Parkinson\u2019s disease (PD), and we have previously shown that astrocytes in substantia nigra (SN) are enriched in AQP4 relative to cortical astrocytes, and that their complement of AQP4 is further increased following treatment with the parkinsonogenic toxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Here, we investigated the effect of Aqp4 deletion on microglial activation in mice subjected to unilateral intrastriatal injection of 1-methyl-4-phenylpyridinium (MPP+, the toxic metabolite of MPTP). Our results show that MPP+ injections lead to a pronounced increase in the expression level of microglial activating genes in the ventral mesencephalon of wild type (WT) mice, but not Aqp4\u2212\/\u2212 mice. We also show, in WT mice, that MPP+ injections cause an upregulation of nigral AQP4 and swelling of astrocytic endfeet. These findings are consistent with the idea that AQP4 plays a pro-inflammatory role in Parkinson\u2019s disease, secondary to the dysregulation of astrocytic volume homeostasis.<\/jats:p>","DOI":"10.3390\/cells9112418","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T09:04:34Z","timestamp":1604567074000},"page":"2418","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Pro-Inflammatory Role of AQP4 in Mice Subjected to Intrastriatal Injections of the Parkinsonogenic Toxin MPP+"],"prefix":"10.3390","volume":"9","author":[{"given":"Agnete","family":"Prydz","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Neuroscience, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1105, Blindern, 0317 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Stahl","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neuroscience, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1105, Blindern, 0317 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soulmaz","family":"Zahl","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neuroscience, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1105, Blindern, 0317 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Skauli","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neuroscience, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1105, Blindern, 0317 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8043-2820","authenticated-orcid":false,"given":"\u00d8ivind","family":"Skare","sequence":"additional","affiliation":[{"name":"Department of Occupational Medicine and Epidemiology, National Institute of Occupational Health, Gydas vei 8, 0363 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole Petter","family":"Ottersen","sequence":"additional","affiliation":[{"name":"President\u2019s Office, Karolinska Institutet, Nobels v\u00e4g 6, 171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1071-1247","authenticated-orcid":false,"given":"Mahmood","family":"Amiry-Moghaddam","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neuroscience, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1105, Blindern, 0317 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1152\/physrev.00011.2013","article-title":"Physiological roles of Aquaporin-4 in brain","volume":"93","author":"Nagelhus","year":"2013","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1002\/jnr.21952","article-title":"Analysis of mice with targeted deletion of AQP9 gene provides conclusive evidence for expression of AQP9 in neurons","volume":"87","author":"Mylonakou","year":"2009","journal-title":"J. Neurosci. 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