Circulatory Astrocyte and Neuronal EVs as Potential Biomarkers of Neurological Dysfunction in HIV-Infected Subjects and Alcohol/Tobacco Users

The diagnosis of neurocognitive disorders associated with HIV infection, alcohol, and tobacco using CSF or neuroimaging are invasive or expensive methods, respectively. Therefore, extracellular vesicles (EVs) can serve as reliable noninvasive markers due to their bidirectional transport of cargo fro...

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Main Authors: Sunitha Kodidela, Kelli Gerth, Namita Sinha, Asit Kumar, Prashant Kumar, Santosh Kumar
Format: Article
Language:English
Published: MDPI AG 2020-05-01
Series:Diagnostics
Subjects:
Online Access:https://www.mdpi.com/2075-4418/10/6/349
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author Sunitha Kodidela
Kelli Gerth
Namita Sinha
Asit Kumar
Prashant Kumar
Santosh Kumar
author_facet Sunitha Kodidela
Kelli Gerth
Namita Sinha
Asit Kumar
Prashant Kumar
Santosh Kumar
author_sort Sunitha Kodidela
collection DOAJ
description The diagnosis of neurocognitive disorders associated with HIV infection, alcohol, and tobacco using CSF or neuroimaging are invasive or expensive methods, respectively. Therefore, extracellular vesicles (EVs) can serve as reliable noninvasive markers due to their bidirectional transport of cargo from the brain to the systemic circulation. Hence, our objective was to investigate the expression of astrocytic (GFAP) and neuronal (L1CAM) specific proteins in EVs circulated in the plasma of HIV subjects, with and without a history of alcohol consumption and tobacco smoking. The protein expression of GFAP (<i>p</i> < 0.01) was significantly enhanced in plasma EVs obtained from HIV-positive subjects and alcohol users compared to healthy subjects, suggesting enhanced activation of astrocytes in those subjects. The L1CAM expression was found to be significantly elevated in cigarette smokers (<i>p</i> < 0.05). However, its expression was not found to be significant in HIV subjects and alcohol users. Both GFAP and L1CAM levels were not further elevated in HIV-positive alcohol or tobacco users compared to HIV-positive nonsubstance users. Taken together, our data demonstrate that the astrocytic and neuronal-specific markers (GFAP and L1CAM) can be packaged in EVs and circulate in plasma, which is further elevated in the presence of HIV infection, alcohol, and/or tobacco. Thus, the astroglial marker GFAP and neuronal marker L1CAM may represent potential biomarkers targeting neurological dysfunction upon HIV infection and/or alcohol/tobacco consumption.
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spelling doaj.art-26904acf02354fb4b6404fd6805c7b362023-11-20T01:59:37ZengMDPI AGDiagnostics2075-44182020-05-0110634910.3390/diagnostics10060349Circulatory Astrocyte and Neuronal EVs as Potential Biomarkers of Neurological Dysfunction in HIV-Infected Subjects and Alcohol/Tobacco UsersSunitha Kodidela0Kelli Gerth1Namita Sinha2Asit Kumar3Prashant Kumar4Santosh Kumar5College of Pharmacy, Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USACollege of Pharmacy, Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USACollege of Pharmacy, Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USACollege of Pharmacy, Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USADepartment of Pediatrics, University of Tennessee Health Science Center and Le Bonheur Children’s Hospital, Memphis, TN 38103, USACollege of Pharmacy, Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USAThe diagnosis of neurocognitive disorders associated with HIV infection, alcohol, and tobacco using CSF or neuroimaging are invasive or expensive methods, respectively. Therefore, extracellular vesicles (EVs) can serve as reliable noninvasive markers due to their bidirectional transport of cargo from the brain to the systemic circulation. Hence, our objective was to investigate the expression of astrocytic (GFAP) and neuronal (L1CAM) specific proteins in EVs circulated in the plasma of HIV subjects, with and without a history of alcohol consumption and tobacco smoking. The protein expression of GFAP (<i>p</i> < 0.01) was significantly enhanced in plasma EVs obtained from HIV-positive subjects and alcohol users compared to healthy subjects, suggesting enhanced activation of astrocytes in those subjects. The L1CAM expression was found to be significantly elevated in cigarette smokers (<i>p</i> < 0.05). However, its expression was not found to be significant in HIV subjects and alcohol users. Both GFAP and L1CAM levels were not further elevated in HIV-positive alcohol or tobacco users compared to HIV-positive nonsubstance users. Taken together, our data demonstrate that the astrocytic and neuronal-specific markers (GFAP and L1CAM) can be packaged in EVs and circulate in plasma, which is further elevated in the presence of HIV infection, alcohol, and/or tobacco. Thus, the astroglial marker GFAP and neuronal marker L1CAM may represent potential biomarkers targeting neurological dysfunction upon HIV infection and/or alcohol/tobacco consumption.https://www.mdpi.com/2075-4418/10/6/349HIVplasma extracellular vesicles (EVs)/exosomesalcoholtobaccoGFAPL1CAM
spellingShingle Sunitha Kodidela
Kelli Gerth
Namita Sinha
Asit Kumar
Prashant Kumar
Santosh Kumar
Circulatory Astrocyte and Neuronal EVs as Potential Biomarkers of Neurological Dysfunction in HIV-Infected Subjects and Alcohol/Tobacco Users
Diagnostics
HIV
plasma extracellular vesicles (EVs)/exosomes
alcohol
tobacco
GFAP
L1CAM
title Circulatory Astrocyte and Neuronal EVs as Potential Biomarkers of Neurological Dysfunction in HIV-Infected Subjects and Alcohol/Tobacco Users
title_full Circulatory Astrocyte and Neuronal EVs as Potential Biomarkers of Neurological Dysfunction in HIV-Infected Subjects and Alcohol/Tobacco Users
title_fullStr Circulatory Astrocyte and Neuronal EVs as Potential Biomarkers of Neurological Dysfunction in HIV-Infected Subjects and Alcohol/Tobacco Users
title_full_unstemmed Circulatory Astrocyte and Neuronal EVs as Potential Biomarkers of Neurological Dysfunction in HIV-Infected Subjects and Alcohol/Tobacco Users
title_short Circulatory Astrocyte and Neuronal EVs as Potential Biomarkers of Neurological Dysfunction in HIV-Infected Subjects and Alcohol/Tobacco Users
title_sort circulatory astrocyte and neuronal evs as potential biomarkers of neurological dysfunction in hiv infected subjects and alcohol tobacco users
topic HIV
plasma extracellular vesicles (EVs)/exosomes
alcohol
tobacco
GFAP
L1CAM
url https://www.mdpi.com/2075-4418/10/6/349
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