{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T18:59:43Z","timestamp":1788980383848,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,8,10]],"date-time":"2016-08-10T00:00:00Z","timestamp":1470787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["81271895\/H1910"],"award-info":[{"award-number":["81271895\/H1910"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Grant-In-Aid for Scientific Research (C) from Japan Society for the Promotion of Science","award":["25461285"],"award-info":[{"award-number":["25461285"]}]},{"name":"Natural Science Foundation of Fujian Province of China","award":["2013J01358"],"award-info":[{"award-number":["2013J01358"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:p>Human immunodeficiency virus (HIV) encephalitis and degeneration of cerebral cortex are established histopathologies of HIV\u2010associated neurocognitive disorders (HAND). We previously reported decreased excitatory amino acid transporter\u20102 (EAAT\u20102) and astrocytic apoptosis in cortical degeneration using SIVmac239 and simian\u2010human immunodeficiency virus (SHIV)\u2010infected macaques and human AIDS autopsy cases. In the present study, we added highly pathogenic SIVsm543\u20103\u2010infected macaques. These animals showed similar degenerative changes in the frontal cortex. Using 11 SIV\u2010infected macaques, three SIVsm543\u20103, five SIVmac239 and three SHIV, we compared brain pathology caused by three different viruses and further analyzed the pathogenic process of HAND. We noticed vacuolar changes in perivascular processes of astrocytes by electron microscopy, and examined expression of astrocyte\u2010specific protein aquaporin\u20104 (AQP4) by immunohistochemistry. APQ4 was diffusely positive in the neuropil and perivascular area in control brains. There was patchy or diffuse decrease of AQP4 staining in the neuropil of SIV\u2010infected macaques, which was associated with EAAT\u20102 staining by double immunostaining. A quantitative analysis demonstrated significant positive correlation between areas of AQP4 and EAAT\u20102. Some astrocytes express EAAT\u20102 but not AQP4, and decrease of EAAT\u20102 expression tended to be less than the decrease of AQP4. Active\u2010caspase\u20103 immunostaining demonstrated apoptosis of neurons and astrocytes in the area of AQP4\/EAAT\u20102 reduction. These results suggest that AQP4 is damaged first and decrease of EAAT\u20102 may follow in pathogenesis of cortical degeneration. This is the first demonstration of decrease of AQP4 and its association with EAAT\u20102 decrease in AIDS brain, suggesting a role in the pathogenesis of HAND.<\/jats:p>","DOI":"10.1111\/neup.12321","type":"journal-article","created":{"date-parts":[[2016,8,10]],"date-time":"2016-08-10T06:27:03Z","timestamp":1470810423000},"page":"25-34","source":"Crossref","is-referenced-by-count":17,"title":["Decrease of aquaporin\u20104 and excitatory amino acid transporter\u20102 indicate astrocyte dysfunction for pathogenesis of cortical degeneration in HIV\u2010associated neurocognitive disorders"],"prefix":"10.1111","volume":"37","author":[{"given":"Hui Qin","family":"Xing","sequence":"first","affiliation":[{"name":"Division of Molecular Pathology, Center for Chronic Viral Diseases Graduate School of Medical and Dental Sciences, Kagoshima University  Kagoshima Japan"},{"name":"Department of Basic Medical Sciences Institute of Neuroscience, Medical College of Xiamen University  Xiamen 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