Increased cortical expression of FK506 binding protein-51 in HIV-associated neurocognitive disorders
FK506 binding protein (FKBP)-51 and FKBP52 act as molecular chaperones to control glucocorticoid receptor (GR) sensitivity. Dysregulation of proteins involved in GR-mediated signaling can lead to maladaptive stress response and aging-related cognitive decline. As HIV infection is related to chronic...
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| Veröffentlicht in: | Journal of neurovirology 2012-08, Vol.18 (4), p.313-322 |
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| creator | Soontornniyomkij, Virawudh Everall, Ian P. Moore, David J. Gouaux, Ben Tatro, Erick T. Gospodarev, Vadim Masliah, Eliezer Yin, Nicole S. Vinters, Harry V. Achim, Cristian L. |
| description | FK506 binding protein (FKBP)-51 and FKBP52 act as molecular chaperones to control glucocorticoid receptor (GR) sensitivity. Dysregulation of proteins involved in GR-mediated signaling can lead to maladaptive stress response and aging-related cognitive decline. As HIV infection is related to chronic stress, we hypothesized that altered cortical expression of these proteins was associated with HIV-associated neurocognitive disorders (HAND). We used quantitative immunohistochemistry to assess expression levels of these proteins in the mid-frontal gyrus of 55 HIV-infected subjects free of cerebral opportunistic diseases compared to 20 age-matched non-HIV controls. The immunoreactivity normalized to the neuroanatomic area measured (IRn) for FKBP51 was increased in HIV subjects both in the cortex and subcortical white matter (
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| doi_str_mv | 10.1007/s13365-011-0076-8 |
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p
< 0.0001,
U
test), while no significant alterations were observed for GR or FKBP52. Notably, the cortical FKBP51 IRn was higher in HAND subjects than in cognitively normal HIV subjects (
p
= 0.02,
U
test). There was also a trend for increasing cortical FKBP51 IRn with the increasing severity of HAND (
p
= 0.08, Kruskal–Wallis test). No significant changes in FKBP51 IRn were found with respect to hepatitis C virus infection, lifetime methamphetamine use, or antiretroviral treatment in HIV subjects. In conclusion, the increased cortical expression of FKBP51 (an inhibitor for GR activity) might represent negative feedback in an attempt to reduce GR sensitivity in the setting of chronic stress-induced elevation of GR-mediated signaling inherent in HIV infection. The further increased FKBP51 expression might lead to maladaptive stress response and HAND.</description><identifier>ISSN: 1355-0284</identifier><identifier>EISSN: 1538-2443</identifier><identifier>DOI: 10.1007/s13365-011-0076-8</identifier><identifier>PMID: 22234543</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Adult ; AIDS Dementia Complex - complications ; AIDS Dementia Complex - drug therapy ; AIDS Dementia Complex - genetics ; AIDS Dementia Complex - metabolism ; Anatomy ; Anti-Retroviral Agents - administration & dosage ; Anti-Retroviral Agents - therapeutic use ; Antiviral agents ; Biomedical and Life Sciences ; Biomedicine ; Case-Control Studies ; Chaperones ; Chronic infection ; Cognition ; Cognitive ability ; Cortex ; Feedback ; Female ; Gene Expression ; Glucocorticoid receptors ; Hand ; Hepacivirus - physiology ; Hepatitis C virus ; Hepatitis C, Chronic - complications ; Hepatitis C, Chronic - drug therapy ; Hepatitis C, Chronic - genetics ; Hepatitis C, Chronic - metabolism ; Human immunodeficiency virus ; Humans ; Immunohistochemistry ; Immunology ; Infectious Diseases ; Male ; Methamphetamine ; Methamphetamine - administration & dosage ; Methamphetamine - adverse effects ; Middle Aged ; Neurology ; Neurosciences ; Parahippocampal Gyrus - metabolism ; Parahippocampal Gyrus - pathology ; Parahippocampal Gyrus - virology ; Signal Transduction - genetics ; Stress ; Stress, Physiological - genetics ; Substance-Related Disorders - complications ; Substance-Related Disorders - genetics ; Substance-Related Disorders - metabolism ; Substantia alba ; Tacrolimus ; Tacrolimus Binding Proteins - genetics ; Tacrolimus Binding Proteins - metabolism ; Tacrolimus-binding protein ; Virology</subject><ispartof>Journal of neurovirology, 2012-08, Vol.18 (4), p.313-322</ispartof><rights>Journal of NeuroVirology, Inc. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-c671b4e7793cd15ba08ae40cf06b4f11de28a86b1084463d243419b18e18d3633</citedby><cites>FETCH-LOGICAL-c475t-c671b4e7793cd15ba08ae40cf06b4f11de28a86b1084463d243419b18e18d3633</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s13365-011-0076-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13365-011-0076-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,315,781,785,886,27928,27929,41492,42561,51323</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22234543$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Soontornniyomkij, Virawudh</creatorcontrib><creatorcontrib>Everall, Ian P.</creatorcontrib><creatorcontrib>Moore, David J.</creatorcontrib><creatorcontrib>Gouaux, Ben</creatorcontrib><creatorcontrib>Tatro, Erick T.</creatorcontrib><creatorcontrib>Gospodarev, Vadim</creatorcontrib><creatorcontrib>Masliah, Eliezer</creatorcontrib><creatorcontrib>Yin, Nicole S.</creatorcontrib><creatorcontrib>Vinters, Harry V.</creatorcontrib><creatorcontrib>Achim, Cristian L.</creatorcontrib><title>Increased cortical expression of FK506 binding protein-51 in HIV-associated neurocognitive disorders</title><title>Journal of neurovirology</title><addtitle>J. Neurovirol</addtitle><addtitle>J Neurovirol</addtitle><description>FK506 binding protein (FKBP)-51 and FKBP52 act as molecular chaperones to control glucocorticoid receptor (GR) sensitivity. Dysregulation of proteins involved in GR-mediated signaling can lead to maladaptive stress response and aging-related cognitive decline. As HIV infection is related to chronic stress, we hypothesized that altered cortical expression of these proteins was associated with HIV-associated neurocognitive disorders (HAND). We used quantitative immunohistochemistry to assess expression levels of these proteins in the mid-frontal gyrus of 55 HIV-infected subjects free of cerebral opportunistic diseases compared to 20 age-matched non-HIV controls. The immunoreactivity normalized to the neuroanatomic area measured (IRn) for FKBP51 was increased in HIV subjects both in the cortex and subcortical white matter (
p
< 0.0001,
U
test), while no significant alterations were observed for GR or FKBP52. Notably, the cortical FKBP51 IRn was higher in HAND subjects than in cognitively normal HIV subjects (
p
= 0.02,
U
test). There was also a trend for increasing cortical FKBP51 IRn with the increasing severity of HAND (
p
= 0.08, Kruskal–Wallis test). No significant changes in FKBP51 IRn were found with respect to hepatitis C virus infection, lifetime methamphetamine use, or antiretroviral treatment in HIV subjects. In conclusion, the increased cortical expression of FKBP51 (an inhibitor for GR activity) might represent negative feedback in an attempt to reduce GR sensitivity in the setting of chronic stress-induced elevation of GR-mediated signaling inherent in HIV infection. The further increased FKBP51 expression might lead to maladaptive stress response and HAND.</description><subject>Adult</subject><subject>AIDS Dementia Complex - complications</subject><subject>AIDS Dementia Complex - drug therapy</subject><subject>AIDS Dementia Complex - genetics</subject><subject>AIDS Dementia Complex - metabolism</subject><subject>Anatomy</subject><subject>Anti-Retroviral Agents - administration & dosage</subject><subject>Anti-Retroviral Agents - therapeutic use</subject><subject>Antiviral agents</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Case-Control Studies</subject><subject>Chaperones</subject><subject>Chronic infection</subject><subject>Cognition</subject><subject>Cognitive ability</subject><subject>Cortex</subject><subject>Feedback</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Glucocorticoid receptors</subject><subject>Hand</subject><subject>Hepacivirus - physiology</subject><subject>Hepatitis C virus</subject><subject>Hepatitis C, Chronic - complications</subject><subject>Hepatitis C, Chronic - drug therapy</subject><subject>Hepatitis C, Chronic - genetics</subject><subject>Hepatitis C, Chronic - metabolism</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunology</subject><subject>Infectious Diseases</subject><subject>Male</subject><subject>Methamphetamine</subject><subject>Methamphetamine - administration & dosage</subject><subject>Methamphetamine - adverse effects</subject><subject>Middle Aged</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Parahippocampal Gyrus - metabolism</subject><subject>Parahippocampal Gyrus - pathology</subject><subject>Parahippocampal Gyrus - virology</subject><subject>Signal Transduction - genetics</subject><subject>Stress</subject><subject>Stress, Physiological - genetics</subject><subject>Substance-Related Disorders - complications</subject><subject>Substance-Related Disorders - genetics</subject><subject>Substance-Related Disorders - metabolism</subject><subject>Substantia alba</subject><subject>Tacrolimus</subject><subject>Tacrolimus Binding Proteins - genetics</subject><subject>Tacrolimus Binding Proteins - metabolism</subject><subject>Tacrolimus-binding protein</subject><subject>Virology</subject><issn>1355-0284</issn><issn>1538-2443</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1vFSEUhonR2A_9AW4MSze0HGAY7sakaVp70yZu1C1h4MyVZi5cYaZp_700t23sxhWQ9z0PhIeQT8BPgPP-tIKUumMcgLWjZuYNOYROGiaUkm_bXnYtFUYdkKNabzkHqYV5Tw6EEFJ1Sh6SsE6-oKsYqM9ljt5NFO93BWuNOdE80svrjms6xBRi2tBdyTPGxDqgMdGr9S_mas0-urkREi4l-7xJcY53SEOsuQQs9QN5N7qp4sen9Zj8vLz4cX7Fbr5_W5-f3TCv-m5mXvcwKOz7lfQBusFx41BxP3I9qBEgoDDO6AG4UUrLIJRUsBrAIJggtZTH5Oueu1uGLQaPaS5usrsSt6482OyifZ2k-Ntu8p2Vslcr6BvgyxOg5D8L1tluY_U4TS5hXqoFrleCCy1Vq8K-6kuuteD4cg1w-2jH7u3YZsc-2rGmzXz-930vE886WkHsC7VFaYPF3ualpPZn_6H-BWCqmzc</recordid><startdate>20120801</startdate><enddate>20120801</enddate><creator>Soontornniyomkij, Virawudh</creator><creator>Everall, Ian P.</creator><creator>Moore, David J.</creator><creator>Gouaux, Ben</creator><creator>Tatro, Erick T.</creator><creator>Gospodarev, Vadim</creator><creator>Masliah, Eliezer</creator><creator>Yin, Nicole S.</creator><creator>Vinters, Harry V.</creator><creator>Achim, Cristian L.</creator><general>Springer US</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>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20120801</creationdate><title>Increased cortical expression of FK506 binding protein-51 in HIV-associated neurocognitive disorders</title><author>Soontornniyomkij, Virawudh ; Everall, Ian P. ; Moore, David J. ; Gouaux, Ben ; Tatro, Erick T. ; Gospodarev, Vadim ; Masliah, Eliezer ; Yin, Nicole S. ; Vinters, Harry V. ; Achim, Cristian L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-c671b4e7793cd15ba08ae40cf06b4f11de28a86b1084463d243419b18e18d3633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>AIDS Dementia Complex - complications</topic><topic>AIDS Dementia Complex - drug therapy</topic><topic>AIDS Dementia Complex - genetics</topic><topic>AIDS Dementia Complex - metabolism</topic><topic>Anatomy</topic><topic>Anti-Retroviral Agents - administration & dosage</topic><topic>Anti-Retroviral Agents - therapeutic use</topic><topic>Antiviral agents</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Case-Control Studies</topic><topic>Chaperones</topic><topic>Chronic infection</topic><topic>Cognition</topic><topic>Cognitive ability</topic><topic>Cortex</topic><topic>Feedback</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Glucocorticoid receptors</topic><topic>Hand</topic><topic>Hepacivirus - physiology</topic><topic>Hepatitis C virus</topic><topic>Hepatitis C, Chronic - complications</topic><topic>Hepatitis C, Chronic - drug therapy</topic><topic>Hepatitis C, Chronic - genetics</topic><topic>Hepatitis C, Chronic - metabolism</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Immunology</topic><topic>Infectious Diseases</topic><topic>Male</topic><topic>Methamphetamine</topic><topic>Methamphetamine - administration & dosage</topic><topic>Methamphetamine - adverse effects</topic><topic>Middle Aged</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Parahippocampal Gyrus - metabolism</topic><topic>Parahippocampal Gyrus - pathology</topic><topic>Parahippocampal Gyrus - virology</topic><topic>Signal Transduction - genetics</topic><topic>Stress</topic><topic>Stress, Physiological - genetics</topic><topic>Substance-Related Disorders - complications</topic><topic>Substance-Related Disorders - genetics</topic><topic>Substance-Related Disorders - metabolism</topic><topic>Substantia alba</topic><topic>Tacrolimus</topic><topic>Tacrolimus Binding Proteins - genetics</topic><topic>Tacrolimus Binding Proteins - metabolism</topic><topic>Tacrolimus-binding protein</topic><topic>Virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Soontornniyomkij, Virawudh</creatorcontrib><creatorcontrib>Everall, Ian P.</creatorcontrib><creatorcontrib>Moore, David J.</creatorcontrib><creatorcontrib>Gouaux, Ben</creatorcontrib><creatorcontrib>Tatro, Erick T.</creatorcontrib><creatorcontrib>Gospodarev, Vadim</creatorcontrib><creatorcontrib>Masliah, Eliezer</creatorcontrib><creatorcontrib>Yin, Nicole S.</creatorcontrib><creatorcontrib>Vinters, Harry V.</creatorcontrib><creatorcontrib>Achim, Cristian L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of neurovirology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Soontornniyomkij, Virawudh</au><au>Everall, Ian P.</au><au>Moore, David J.</au><au>Gouaux, Ben</au><au>Tatro, Erick T.</au><au>Gospodarev, Vadim</au><au>Masliah, Eliezer</au><au>Yin, Nicole S.</au><au>Vinters, Harry V.</au><au>Achim, Cristian L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased cortical expression of FK506 binding protein-51 in HIV-associated neurocognitive disorders</atitle><jtitle>Journal of neurovirology</jtitle><stitle>J. Neurovirol</stitle><addtitle>J Neurovirol</addtitle><date>2012-08-01</date><risdate>2012</risdate><volume>18</volume><issue>4</issue><spage>313</spage><epage>322</epage><pages>313-322</pages><issn>1355-0284</issn><eissn>1538-2443</eissn><abstract>FK506 binding protein (FKBP)-51 and FKBP52 act as molecular chaperones to control glucocorticoid receptor (GR) sensitivity. Dysregulation of proteins involved in GR-mediated signaling can lead to maladaptive stress response and aging-related cognitive decline. As HIV infection is related to chronic stress, we hypothesized that altered cortical expression of these proteins was associated with HIV-associated neurocognitive disorders (HAND). We used quantitative immunohistochemistry to assess expression levels of these proteins in the mid-frontal gyrus of 55 HIV-infected subjects free of cerebral opportunistic diseases compared to 20 age-matched non-HIV controls. The immunoreactivity normalized to the neuroanatomic area measured (IRn) for FKBP51 was increased in HIV subjects both in the cortex and subcortical white matter (
p
< 0.0001,
U
test), while no significant alterations were observed for GR or FKBP52. Notably, the cortical FKBP51 IRn was higher in HAND subjects than in cognitively normal HIV subjects (
p
= 0.02,
U
test). There was also a trend for increasing cortical FKBP51 IRn with the increasing severity of HAND (
p
= 0.08, Kruskal–Wallis test). No significant changes in FKBP51 IRn were found with respect to hepatitis C virus infection, lifetime methamphetamine use, or antiretroviral treatment in HIV subjects. In conclusion, the increased cortical expression of FKBP51 (an inhibitor for GR activity) might represent negative feedback in an attempt to reduce GR sensitivity in the setting of chronic stress-induced elevation of GR-mediated signaling inherent in HIV infection. The further increased FKBP51 expression might lead to maladaptive stress response and HAND.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>22234543</pmid><doi>10.1007/s13365-011-0076-8</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of neurovirology, 2012-08, Vol.18 (4), p.313-322 |
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| subjects | Adult AIDS Dementia Complex - complications AIDS Dementia Complex - drug therapy AIDS Dementia Complex - genetics AIDS Dementia Complex - metabolism Anatomy Anti-Retroviral Agents - administration & dosage Anti-Retroviral Agents - therapeutic use Antiviral agents Biomedical and Life Sciences Biomedicine Case-Control Studies Chaperones Chronic infection Cognition Cognitive ability Cortex Feedback Female Gene Expression Glucocorticoid receptors Hand Hepacivirus - physiology Hepatitis C virus Hepatitis C, Chronic - complications Hepatitis C, Chronic - drug therapy Hepatitis C, Chronic - genetics Hepatitis C, Chronic - metabolism Human immunodeficiency virus Humans Immunohistochemistry Immunology Infectious Diseases Male Methamphetamine Methamphetamine - administration & dosage Methamphetamine - adverse effects Middle Aged Neurology Neurosciences Parahippocampal Gyrus - metabolism Parahippocampal Gyrus - pathology Parahippocampal Gyrus - virology Signal Transduction - genetics Stress Stress, Physiological - genetics Substance-Related Disorders - complications Substance-Related Disorders - genetics Substance-Related Disorders - metabolism Substantia alba Tacrolimus Tacrolimus Binding Proteins - genetics Tacrolimus Binding Proteins - metabolism Tacrolimus-binding protein Virology |
| title | Increased cortical expression of FK506 binding protein-51 in HIV-associated neurocognitive disorders |
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