{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:29:58Z","timestamp":1790206198507,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,6,13]],"date-time":"2017-06-13T00:00:00Z","timestamp":1497312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DA007606"],"award-info":[{"award-number":["DA007606"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DA 033966"],"award-info":[{"award-number":["R01 DA 033966"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS060632"],"award-info":[{"award-number":["R01 NS060632"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS084817"],"award-info":[{"award-number":["R01 NS084817"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Emerging evidence suggests that cell senescence plays an important role in aging\u2010associated diseases including neurodegenerative diseases. <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> leads to a spectrum of neurologic diseases collectively termed <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010associated neurocognitive disorders (<jats:styled-content style=\"fixed-case\">HAND<\/jats:styled-content>). Drug abuse, particularly methamphetamine (meth), is a frequently abused psychostimulant among <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>+ individuals and its abuse exacerbates <jats:styled-content style=\"fixed-case\">HAND<\/jats:styled-content>. The mechanism by which <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> and meth lead to brain cell dysregulation is not entirely clear. In this study, we evaluated the impact of <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> and meth on astrocyte senescence using <jats:italic>in\u00a0vitro<\/jats:italic> and several animal models. Astrocytes constitute up to 50% of brain cells and play a pivotal role in marinating brain homeostasis. We show here that <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> and meth induce significant senescence of primary human fetal astrocytes, as evaluated by induction of senescence markers (\u03b2\u2010galactosidase and p16<jats:styled-content style=\"fixed-case\"><jats:sup>INK<\/jats:sup><\/jats:styled-content><jats:sup>4A<\/jats:sup>), senescence\u2010associated morphologic changes, and cell cycle arrest. <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010 and meth\u2010mediated astrocyte senescence was also demonstrated in three small animal models (humanized mouse model of <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">NSG<\/jats:styled-content>\u2010hu<jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content>s, <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010transgenic rats, and in a meth administration rat model). Senescent astrocytes in turn mediated neuronal toxicity. Further, we show that \u03b2\u2010catenin, a pro\u2010survival\/proliferation transcriptional co\u2010activator, is downregulated by <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> and meth in human astrocytes and this downregulation promotes astrocyte senescence while induction of \u03b2\u2010catenin blocks <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010 and meth\u2010mediated astrocyte senescence. These studies, for the first time, demonstrate that <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> and meth induce astrocyte senescence and implicate the \u03b2\u2010catenin pathway as potential therapeutic target to overcome astrocyte senescence.<\/jats:p>","DOI":"10.1111\/acel.12593","type":"journal-article","created":{"date-parts":[[2017,6,14]],"date-time":"2017-06-14T04:08:58Z","timestamp":1497413338000},"page":"956-965","source":"Crossref","is-referenced-by-count":57,"title":["<scp>HIV<\/scp> and drug abuse mediate astrocyte senescence in a \u03b2\u2010catenin\u2010dependent manner leading to neuronal toxicity"],"prefix":"10.1111","volume":"16","author":[{"given":"Chunjiang","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology Rush University Medical Center Chicago IL 60612 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivas D.","family":"Narasipura","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology Rush University Medical Center Chicago IL 60612 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen H.","family":"Richards","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology Rush University Medical Center Chicago IL 60612 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu\u2010Ti","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Rush University Medical Center Chicago IL 60612 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Indiana University School of Medicine Indianapolis IN 46202 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Al\u2010Harthi","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology Rush University Medical Center Chicago IL 60612 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2784"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-012-9412-x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10600"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-5428(06)80254-8"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20120122"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0045069"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.10.027"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-030212-183653"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000240066.02404.e6"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12029"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2012.05.004"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.450107"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.06023-11"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12631"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2530-12.2012"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3145-12.2012"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/10550880802122554"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-012-9417-5"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/13803390903512637"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0109603"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa5612"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.039"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00126334-200312150-00004"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2015.05.014"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100099"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3404-07.2007"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(02)00207-1"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06266-11"},{"issue":"2","key":"e_1_2_7_30_1","doi-asserted-by":"crossref","first-page":"S62","DOI":"10.1097\/00126334-200210012-00006","article-title":"Molecular basis for interactions of HIV and drugs of abuse","volume":"31","author":"Nath A","year":"2002","journal-title":"J. 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