{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:36:26Z","timestamp":1792182986973,"version":"4.4.0"},"reference-count":61,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,11,13]],"date-time":"2013-11-13T00:00:00Z","timestamp":1384300800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human immunodeficiency virus\u20101 (<jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>) is a public health issue and a major complication of the disease is Neuro<jats:styled-content style=\"fixed-case\">AIDS<\/jats:styled-content>. <jats:italic>In vivo<\/jats:italic>, microglia\/macrophages are the main cells infected. However, a low but significant number of <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010infected astrocytes has also been detected, but their role in the pathogenesis of Neuro<jats:styled-content style=\"fixed-case\">AIDS<\/jats:styled-content> is not well understood. Our previous data indicate that gap junction channels amplify toxicity from few <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010infected into uninfected astrocytes. Now, we demonstrated that <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> infection of astrocytes results in the opening of connexin43 hemichannels (HCs). <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010induced opening of connexin43 <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>s resulted in dysregulated secretion of dickkopf\u20101 protein (<jats:styled-content style=\"fixed-case\">DKK<\/jats:styled-content>1, a soluble wnt pathway inhibitor). Treatment of mixed cultures of neurons and astrocytes with <jats:styled-content style=\"fixed-case\">DKK<\/jats:styled-content>1, in the absence of <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> infection, resulted in the collapse of neuronal processes. <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> infection of mixed cultures of human neurons and astrocytes also resulted in the collapse of neuronal processes through a <jats:styled-content style=\"fixed-case\">DKK<\/jats:styled-content>1\u2010dependent mechanism. In addition, dysregulated <jats:styled-content style=\"fixed-case\">DKK<\/jats:styled-content>1 expression in astrocytes was observed in human brain tissue sections of individuals with <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> encephalitis as compared to tissue sections from uninfected individuals. Thus, we demonstrated that <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> infection of astrocytes induces dysregulation of <jats:styled-content style=\"fixed-case\">DKK<\/jats:styled-content>1 by a <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>\u2010dependent mechanism that contributes to the brain pathogenesis observed in <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010infected individuals.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12492-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>Our studies demonstrated that HIV infection of astrocytes, despite minimal replication and a low number of infected cells, induces dysregulation of DKK1 secretion by a Cx43 hemichannel (HC)\u2010dependent mechanism. Enhanced DKK1 secretion in response to HIV infection of glial cells compromised formation and stability of neuronal processes, similar to the synaptic compromise observed in HIV\u2010infected individuals. In addition, analysis of human brain tissue sections obtained from encephalitic individuals also shows enhanced expression of DKK1 in astrocytes. Our data provide a novel mechanism by which HIV infection of glial cells participate in the pathogenesis of brain dysfunction observed in HIV\u2010infected individuals. LRP5\u00a0=\u00a0Low\u2010density lipoprotein receptor\u2010related protein 5.<\/jats:p>","DOI":"10.1111\/jnc.12492","type":"journal-article","created":{"date-parts":[[2013,10,18]],"date-time":"2013-10-18T08:21:20Z","timestamp":1382084480000},"page":"752-763","source":"Crossref","is-referenced-by-count":68,"title":["<scp>HIV<\/scp> increases the release of dickkopf\u20101 protein from human astrocytes by a Cx43 hemichannel\u2010dependent mechanism"],"prefix":"10.1111","volume":"128","author":[{"given":"Juan Andres","family":"Orellana","sequence":"first","affiliation":[{"name":"Public Health Research Institute (PHRI) Rutgers New Jersey Medical School Rutgers The State University of New Jersey Newark New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"S\u00e1ez","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda Pontificia Universidad Cat\u00f3lica de Chile Santiago Chile"},{"name":"Centro Interdisciplinario de Neurociencias de Valpara\u00edso Valpara\u00edso Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Vander Lann","family":"Bennett","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Albert Einstein College of Medicine Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan Weinberger","family":"Berman","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine Bronx New York USA"},{"name":"Department of Microbiology and Immunology Albert Einstein College of Medicine Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Morgello","sequence":"additional","affiliation":[{"name":"Department of Neurology Mount Sinai Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliseo Alberto","family":"Eugenin","sequence":"additional","affiliation":[{"name":"Public Health Research Institute (PHRI) Rutgers New Jersey Medical School Rutgers The State University of New Jersey Newark New Jersey USA"},{"name":"Department of Microbiology and Molecular Genetics Rutgers New Jersey Medical School Rutgers The State University of New Jersey Newark New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,11,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401901"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7798"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-012-9411-y"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010051113"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2990.2003.00475.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2012.08.042"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2008.04.002"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.01055.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5230-04.2005"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2012.00013"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81313-6"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-5428(06)80269-X"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2002.tb00461.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/381667a0"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/15419060802198587"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.65.4.453"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1046-2023(02)00359-6"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4154-07.2007"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01775.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611699104"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1460-11.2011"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-012-9352-5"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20060175"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnene.2010.00129"},{"key":"e_1_2_8_26_1","first-page":"39","article-title":"Novel mechanisms of central nervous system damage in HIV infection","volume":"2","author":"Hazleton J. 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