Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats
The integrity and function of the gut is impaired in HIV-infected individuals, and gut pathogenesis may play a role in several HIV-associated disorders. Methamphetamine is a popular illicit drug abused by HIV-infected individuals. However, the effect of methamphetamine on the gut and its potential t...
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| Veröffentlicht in: | PloS one 2018-01, Vol.13 (1), p.e0190078-e0190078 |
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| creator | Persons, Amanda L Bradaric, Brinda D Dodiya, Hemraj B Ohene-Nyako, Michael Forsyth, Christopher B Keshavarzian, Ali Shaikh, Maliha Napier, T Celeste |
| description | The integrity and function of the gut is impaired in HIV-infected individuals, and gut pathogenesis may play a role in several HIV-associated disorders. Methamphetamine is a popular illicit drug abused by HIV-infected individuals. However, the effect of methamphetamine on the gut and its potential to exacerbate HIV-associated gut pathology is not known. To shed light on this scenario, we evaluated colon barrier pathology in a rat model of the human comorbid condition. Intestinal barrier integrity and permeability were assessed in drug-naïve Fischer 344 HIV-1 transgenic (Tg) and non-Tg rats, and in Tg and non-Tg rats instrumented with jugular cannulae trained to self-administer methamphetamine or serving as saline-yoked controls. Intestinal permeability was determined by measuring the urine content of orally gavaged sugars. Intestinal barrier integrity was evaluated by immunoblotting or immunofluorescence of colon claudin-1 and zonula occludens-1 (ZO-1), two major tight junction proteins that regulate gut epithelial paracellular permeability. Both non-Tg and Tg rats self-administered moderate amounts of methamphetamine. These amounts were sufficient to increase colon permeability, reduce protein level of claudin-1, and reduce claudin-1 and ZO-1 immunofluorescence in Tg rats relative to non-Tg rats. Methamphetamine decreased tight junction immunofluorescence in non-Tg rats, with a similar, but non-significant trend observed in Tg rats. However, the effect of methamphetamine on tight junction proteins was subthreshold to gut leakiness. These findings reveal that both HIV-1 proteins and methamphetamine alter colon barrier integrity, and indicate that the gut may be a pathogenic site for these insults. |
| doi_str_mv | 10.1371/journal.pone.0190078 |
| format | Article |
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Methamphetamine is a popular illicit drug abused by HIV-infected individuals. However, the effect of methamphetamine on the gut and its potential to exacerbate HIV-associated gut pathology is not known. To shed light on this scenario, we evaluated colon barrier pathology in a rat model of the human comorbid condition. Intestinal barrier integrity and permeability were assessed in drug-naïve Fischer 344 HIV-1 transgenic (Tg) and non-Tg rats, and in Tg and non-Tg rats instrumented with jugular cannulae trained to self-administer methamphetamine or serving as saline-yoked controls. Intestinal permeability was determined by measuring the urine content of orally gavaged sugars. Intestinal barrier integrity was evaluated by immunoblotting or immunofluorescence of colon claudin-1 and zonula occludens-1 (ZO-1), two major tight junction proteins that regulate gut epithelial paracellular permeability. Both non-Tg and Tg rats self-administered moderate amounts of methamphetamine. These amounts were sufficient to increase colon permeability, reduce protein level of claudin-1, and reduce claudin-1 and ZO-1 immunofluorescence in Tg rats relative to non-Tg rats. Methamphetamine decreased tight junction immunofluorescence in non-Tg rats, with a similar, but non-significant trend observed in Tg rats. However, the effect of methamphetamine on tight junction proteins was subthreshold to gut leakiness. These findings reveal that both HIV-1 proteins and methamphetamine alter colon barrier integrity, and indicate that the gut may be a pathogenic site for these insults.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0190078</identifier><identifier>PMID: 29293553</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Addictions ; Animals ; Biology and Life Sciences ; Blood-brain barrier ; Cannulae ; Cocaine ; Colon ; Colon - physiopathology ; Comorbidity ; Digestive system ; Digestive tract ; Dosage and administration ; Drug abuse ; Drug therapy ; Gastrointestinal tract ; Genetic engineering ; Genotype ; HIV ; HIV infections ; HIV Infections - complications ; HIV Infections - physiopathology ; HIV-1 - genetics ; Human immunodeficiency virus ; Hypotheses ; Immunoblotting ; Immunofluorescence ; Inflammation ; Integrity ; Internal medicine ; Intestinal Mucosa - physiopathology ; Intestine ; Male ; Medicine and Health Sciences ; Methamphetamine ; Methamphetamine - administration & dosage ; Neurosciences ; Nutrition ; Parkinson's disease ; Pathogenesis ; Pathology ; Permeability ; Pharmacology ; Physical Sciences ; Proteins ; Rats ; Rats, Inbred F344 ; Rats, Transgenic ; Research and Analysis Methods ; Rodents ; Self Administration ; Sugar ; Urine ; Zonula occludens-1 protein</subject><ispartof>PloS one, 2018-01, Vol.13 (1), p.e0190078-e0190078</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Persons et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Persons et al 2018 Persons et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c641t-2963de1b0a04ea08a130cb38eac83d85bfd7c7ac583978ffac1b2191a8de80803</cites><orcidid>0000-0002-8494-3721</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749763/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749763/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29293553$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Buch, Shilpa J.</contributor><creatorcontrib>Persons, Amanda L</creatorcontrib><creatorcontrib>Bradaric, Brinda D</creatorcontrib><creatorcontrib>Dodiya, Hemraj B</creatorcontrib><creatorcontrib>Ohene-Nyako, Michael</creatorcontrib><creatorcontrib>Forsyth, Christopher B</creatorcontrib><creatorcontrib>Keshavarzian, Ali</creatorcontrib><creatorcontrib>Shaikh, Maliha</creatorcontrib><creatorcontrib>Napier, T Celeste</creatorcontrib><title>Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The integrity and function of the gut is impaired in HIV-infected individuals, and gut pathogenesis may play a role in several HIV-associated disorders. Methamphetamine is a popular illicit drug abused by HIV-infected individuals. However, the effect of methamphetamine on the gut and its potential to exacerbate HIV-associated gut pathology is not known. To shed light on this scenario, we evaluated colon barrier pathology in a rat model of the human comorbid condition. Intestinal barrier integrity and permeability were assessed in drug-naïve Fischer 344 HIV-1 transgenic (Tg) and non-Tg rats, and in Tg and non-Tg rats instrumented with jugular cannulae trained to self-administer methamphetamine or serving as saline-yoked controls. Intestinal permeability was determined by measuring the urine content of orally gavaged sugars. Intestinal barrier integrity was evaluated by immunoblotting or immunofluorescence of colon claudin-1 and zonula occludens-1 (ZO-1), two major tight junction proteins that regulate gut epithelial paracellular permeability. Both non-Tg and Tg rats self-administered moderate amounts of methamphetamine. These amounts were sufficient to increase colon permeability, reduce protein level of claudin-1, and reduce claudin-1 and ZO-1 immunofluorescence in Tg rats relative to non-Tg rats. Methamphetamine decreased tight junction immunofluorescence in non-Tg rats, with a similar, but non-significant trend observed in Tg rats. However, the effect of methamphetamine on tight junction proteins was subthreshold to gut leakiness. These findings reveal that both HIV-1 proteins and methamphetamine alter colon barrier integrity, and indicate that the gut may be a pathogenic site for these insults.</description><subject>Addictions</subject><subject>Animals</subject><subject>Biology and Life Sciences</subject><subject>Blood-brain barrier</subject><subject>Cannulae</subject><subject>Cocaine</subject><subject>Colon</subject><subject>Colon - physiopathology</subject><subject>Comorbidity</subject><subject>Digestive system</subject><subject>Digestive tract</subject><subject>Dosage and administration</subject><subject>Drug abuse</subject><subject>Drug therapy</subject><subject>Gastrointestinal tract</subject><subject>Genetic engineering</subject><subject>Genotype</subject><subject>HIV</subject><subject>HIV infections</subject><subject>HIV Infections - complications</subject><subject>HIV Infections - physiopathology</subject><subject>HIV-1 - genetics</subject><subject>Human immunodeficiency virus</subject><subject>Hypotheses</subject><subject>Immunoblotting</subject><subject>Immunofluorescence</subject><subject>Inflammation</subject><subject>Integrity</subject><subject>Internal medicine</subject><subject>Intestinal Mucosa - physiopathology</subject><subject>Intestine</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Methamphetamine</subject><subject>Methamphetamine - administration & dosage</subject><subject>Neurosciences</subject><subject>Nutrition</subject><subject>Parkinson's disease</subject><subject>Pathogenesis</subject><subject>Pathology</subject><subject>Permeability</subject><subject>Pharmacology</subject><subject>Physical Sciences</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Rats, Transgenic</subject><subject>Research and Analysis Methods</subject><subject>Rodents</subject><subject>Self Administration</subject><subject>Sugar</subject><subject>Urine</subject><subject>Zonula occludens-1 protein</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkktr3DAUhU1paR7tPyitoRDahaeS5Ye0KYShbQYCA31kK64l2aNBliaWXJp_X03GCeOSRfHCkvydc3WvT5K8wWiBSY0_bd04WDCLnbNqgTBDqKbPklPMSJ5VOSLPj9YnyZn3W4RKQqvqZXKSs5yRsiSnyXrpjLOpvPOD6kYDQcedtmmvwgb63UYF6LVVqVemzUDGtfZBDdp26dXqJsNpGMD6Tlkt0gGCf5W8aMF49Xp6nye_vn75ubzKrtffVsvL60xUBQ5ZzioiFW4QoEIBooAJEg2hCgQlkpZNK2tRgygpYTVtWxC4yTHDQKWiiCJynrw7-O6M83yaheeYRQHCJakisToQ0sGW7wbdw3DHHWh-f-CGjsMQtDCKE1QgmZOqRrIpSM2oLMo8LysFtC6ohOj1eao2Nr2SQtnYtpmZzr9YveGd-83LumB1RaLBh8lgcLej8oH32gtlDFjlxvt7F3kVp8Ii-v4f9OnuJqqD2IC2rYt1xd6UX5Y5xpixikZq8QQVH6l6LWJwWh3PZ4KPM0FkgvoTOhi956sf3_-fXd_M2YsjdqPAhI13ZtzHzc_B4gCKwfmYyfZxyBjxfe4fpsH3uedT7qPs7fEPehQ9BJ38BRQ0_Mk</recordid><startdate>20180102</startdate><enddate>20180102</enddate><creator>Persons, Amanda L</creator><creator>Bradaric, Brinda D</creator><creator>Dodiya, Hemraj B</creator><creator>Ohene-Nyako, Michael</creator><creator>Forsyth, Christopher B</creator><creator>Keshavarzian, Ali</creator><creator>Shaikh, Maliha</creator><creator>Napier, T Celeste</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-8494-3721</orcidid></search><sort><creationdate>20180102</creationdate><title>Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats</title><author>Persons, Amanda L ; Bradaric, Brinda D ; Dodiya, Hemraj B ; Ohene-Nyako, Michael ; Forsyth, Christopher B ; Keshavarzian, Ali ; Shaikh, Maliha ; Napier, T Celeste</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c641t-2963de1b0a04ea08a130cb38eac83d85bfd7c7ac583978ffac1b2191a8de80803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Addictions</topic><topic>Animals</topic><topic>Biology and Life Sciences</topic><topic>Blood-brain barrier</topic><topic>Cannulae</topic><topic>Cocaine</topic><topic>Colon</topic><topic>Colon - 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Methamphetamine is a popular illicit drug abused by HIV-infected individuals. However, the effect of methamphetamine on the gut and its potential to exacerbate HIV-associated gut pathology is not known. To shed light on this scenario, we evaluated colon barrier pathology in a rat model of the human comorbid condition. Intestinal barrier integrity and permeability were assessed in drug-naïve Fischer 344 HIV-1 transgenic (Tg) and non-Tg rats, and in Tg and non-Tg rats instrumented with jugular cannulae trained to self-administer methamphetamine or serving as saline-yoked controls. Intestinal permeability was determined by measuring the urine content of orally gavaged sugars. Intestinal barrier integrity was evaluated by immunoblotting or immunofluorescence of colon claudin-1 and zonula occludens-1 (ZO-1), two major tight junction proteins that regulate gut epithelial paracellular permeability. Both non-Tg and Tg rats self-administered moderate amounts of methamphetamine. These amounts were sufficient to increase colon permeability, reduce protein level of claudin-1, and reduce claudin-1 and ZO-1 immunofluorescence in Tg rats relative to non-Tg rats. Methamphetamine decreased tight junction immunofluorescence in non-Tg rats, with a similar, but non-significant trend observed in Tg rats. However, the effect of methamphetamine on tight junction proteins was subthreshold to gut leakiness. These findings reveal that both HIV-1 proteins and methamphetamine alter colon barrier integrity, and indicate that the gut may be a pathogenic site for these insults.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29293553</pmid><doi>10.1371/journal.pone.0190078</doi><orcidid>https://orcid.org/0000-0002-8494-3721</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2018-01, Vol.13 (1), p.e0190078-e0190078 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1983901536 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Addictions Animals Biology and Life Sciences Blood-brain barrier Cannulae Cocaine Colon Colon - physiopathology Comorbidity Digestive system Digestive tract Dosage and administration Drug abuse Drug therapy Gastrointestinal tract Genetic engineering Genotype HIV HIV infections HIV Infections - complications HIV Infections - physiopathology HIV-1 - genetics Human immunodeficiency virus Hypotheses Immunoblotting Immunofluorescence Inflammation Integrity Internal medicine Intestinal Mucosa - physiopathology Intestine Male Medicine and Health Sciences Methamphetamine Methamphetamine - administration & dosage Neurosciences Nutrition Parkinson's disease Pathogenesis Pathology Permeability Pharmacology Physical Sciences Proteins Rats Rats, Inbred F344 Rats, Transgenic Research and Analysis Methods Rodents Self Administration Sugar Urine Zonula occludens-1 protein |
| title | Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T21%3A48%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Colon%20dysregulation%20in%20methamphetamine%20self-administering%20HIV-1%20transgenic%20rats&rft.jtitle=PloS%20one&rft.au=Persons,%20Amanda%20L&rft.date=2018-01-02&rft.volume=13&rft.issue=1&rft.spage=e0190078&rft.epage=e0190078&rft.pages=e0190078-e0190078&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0190078&rft_dat=%3Cgale_plos_%3EA521119968%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1983901536&rft_id=info:pmid/29293553&rft_galeid=A521119968&rft_doaj_id=oai_doaj_org_article_3040d23670db43798d452256ea8748da&rfr_iscdi=true |