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Journal article
Telomere Length Shortening in Microglia: Implication for Accelerated Senescence and Neurocognitive Deficits in HIV
Vaccines (Basel), v 9(7), p721
01 Jul 2021
PMID: 34358137
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The widespread use of combination antiretroviral therapy (cART) has led to the accelerated aging of the HIV-infected population, and these patients continue to have a range of mild to moderate HIV-associated neurocognitive disorders (HAND). Infection results in altered mitochondrial function. The HIV-1 viral protein Tat significantly alters mtDNA content and enhances oxidative stress in immune cells. Microglia are the immune cells of the central nervous system (CNS) that exhibit a significant mitotic potential and are thus susceptible to telomere shortening. HIV disrupts the normal interplay between microglia and neurons, thereby inducing neurodegeneration. HIV cART contributes to the inhibition of telomerase activity and premature telomere shortening in activated peripheral blood mononuclear cells (PBMC). However, limited information is available on the effect of cART on telomere length (TL) in microglia. Although it is well established that telomere shortening induces cell senescence and contributes to the development of age-related neuro-pathologies, the effect of HIV-Tat on telomere length in human microglial cells and its potential contribution to HAND are not well understood. It is speculated that in HAND intrinsic molecular mechanisms that control energy production underlie microglia-mediated neuronal injury. TL, telomerase and mtDNA expression were quantified in microglial cells using real time PCR. Cellular energetics were measured using the Seahorse assay. The changes in mitochondrial function were examined by Raman Spectroscopy. We have also examined TL in the PBMC obtained from HIV-1 infected rapid progressors (RP) on cART and those who were cART naive, and observed a significant decrease in telomere length in RP on cART as compared to RP's who were cART naive. We observed a significant decrease in telomerase activity, telomere length and mitochondrial function, and an increase in oxidative stress in human microglial cells treated with HIV Tat. Neurocognitive impairment in HIV disease may in part be due to accelerated neuro-pathogenesis in microglial cells, which is attributable to increased oxidative stress and mitochondrial dysfunction.
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Details
- Title
- Telomere Length Shortening in Microglia: Implication for Accelerated Senescence and Neurocognitive Deficits in HIV
- Creators
- Chiu-Bin Hsiao - Allegheny General HospitalHarneet Bedi - Department of Medicine, Division of Allergy, Immunology & Rheumatology, University at Buffalo's Clinical Translational Research Center, Buffalo, NY 14203, USA.Raquel Gomez - Department of Medicine, Division of Allergy, Immunology & Rheumatology, University at Buffalo's Clinical Translational Research Center, Buffalo, NY 14203, USA.Ayesha Khan - Department of Medicine, Division of Allergy, Immunology & Rheumatology, University at Buffalo's Clinical Translational Research Center, Buffalo, NY 14203, USA.Taylor Meciszewski - Department of Medicine, Division of Allergy, Immunology & Rheumatology, University at Buffalo's Clinical Translational Research Center, Buffalo, NY 14203, USA.Ravikumar Aalinkeel - Department of Medicine, Division of Allergy, Immunology & Rheumatology, University at Buffalo's Clinical Translational Research Center, Buffalo, NY 14203, USA.Ting Chean Khoo - University at Albany, State University of New YorkAnna Sharikova - University at Albany, State University of New YorkAlexander Khmaladze - University at Albany, State University of New YorkSupriya D. Mahajan - Department of Medicine, Division of Allergy, Immunology & Rheumatology, University at Buffalo's Clinical Translational Research Center, Buffalo, NY 14203, USA.
- Publication Details
- Vaccines (Basel), v 9(7), p721
- Publisher
- Mdpi
- Number of pages
- 17
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Medicine (Graduate)
- Web of Science ID
- WOS:000677173300001
- Scopus ID
- 2-s2.0-85109493877
- Other Identifier
- 991019169496504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology
- Medicine, Research & Experimental