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Brain tissue transcriptomic analysis of SIV-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis and poly (ADP-ribose) polymerases (PARPs) as potential therapeutic targets

Despite improvements in antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders (HAND) remain prevalent in subjects undergoing therapy. HAND significantly affects individuals’ quality of life, as well as adherence to therapy, and, despite the increasin...

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Autores principales: Mavian, Carla, Ramirez-Mata, Andrea S., Dollar, James Jarad, Nolan, David J., Cash, Melanie, White, Kevin, Rich, Shannan N., Magalis, Brittany Rife, Marini, Simone, Prosperi, Mattia C. F., Amador, David Moraga, Riva, Alberto, Williams, Kenneth C., Salemi, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786889/
https://www.ncbi.nlm.nih.gov/pubmed/33405206
http://dx.doi.org/10.1007/s13365-020-00927-z
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author Mavian, Carla
Ramirez-Mata, Andrea S.
Dollar, James Jarad
Nolan, David J.
Cash, Melanie
White, Kevin
Rich, Shannan N.
Magalis, Brittany Rife
Marini, Simone
Prosperi, Mattia C. F.
Amador, David Moraga
Riva, Alberto
Williams, Kenneth C.
Salemi, Marco
author_facet Mavian, Carla
Ramirez-Mata, Andrea S.
Dollar, James Jarad
Nolan, David J.
Cash, Melanie
White, Kevin
Rich, Shannan N.
Magalis, Brittany Rife
Marini, Simone
Prosperi, Mattia C. F.
Amador, David Moraga
Riva, Alberto
Williams, Kenneth C.
Salemi, Marco
author_sort Mavian, Carla
collection PubMed
description Despite improvements in antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders (HAND) remain prevalent in subjects undergoing therapy. HAND significantly affects individuals’ quality of life, as well as adherence to therapy, and, despite the increasing understanding of neuropathogenesis, no definitive diagnostic or prognostic marker has been identified. We investigated transcriptomic profiles in frontal cortex tissues of Simian immunodeficiency virus (SIV)-infected Rhesus macaques sacrificed at different stages of infection. Gene expression was compared among SIV-infected animals (n = 11), with or without CD8+ lymphocyte depletion, based on detectable (n = 6) or non-detectable (n = 5) presence of the virus in frontal cortex tissues. Significant enrichment in activation of monocyte and macrophage cellular pathways was found in animals with detectable brain infection, independently from CD8+ lymphocyte depletion. In addition, transcripts of four poly (ADP-ribose) polymerases (PARPs) were up-regulated in the frontal cortex, which was confirmed by real-time polymerase chain reaction. Our results shed light on involvement of PARPs in SIV infection of the brain and their role in SIV-associated neurodegenerative processes. Inhibition of PARPs may provide an effective novel therapeutic target for HIV-related neuropathology.
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spelling pubmed-77868892021-01-06 Brain tissue transcriptomic analysis of SIV-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis and poly (ADP-ribose) polymerases (PARPs) as potential therapeutic targets Mavian, Carla Ramirez-Mata, Andrea S. Dollar, James Jarad Nolan, David J. Cash, Melanie White, Kevin Rich, Shannan N. Magalis, Brittany Rife Marini, Simone Prosperi, Mattia C. F. Amador, David Moraga Riva, Alberto Williams, Kenneth C. Salemi, Marco J Neurovirol Article Despite improvements in antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders (HAND) remain prevalent in subjects undergoing therapy. HAND significantly affects individuals’ quality of life, as well as adherence to therapy, and, despite the increasing understanding of neuropathogenesis, no definitive diagnostic or prognostic marker has been identified. We investigated transcriptomic profiles in frontal cortex tissues of Simian immunodeficiency virus (SIV)-infected Rhesus macaques sacrificed at different stages of infection. Gene expression was compared among SIV-infected animals (n = 11), with or without CD8+ lymphocyte depletion, based on detectable (n = 6) or non-detectable (n = 5) presence of the virus in frontal cortex tissues. Significant enrichment in activation of monocyte and macrophage cellular pathways was found in animals with detectable brain infection, independently from CD8+ lymphocyte depletion. In addition, transcripts of four poly (ADP-ribose) polymerases (PARPs) were up-regulated in the frontal cortex, which was confirmed by real-time polymerase chain reaction. Our results shed light on involvement of PARPs in SIV infection of the brain and their role in SIV-associated neurodegenerative processes. Inhibition of PARPs may provide an effective novel therapeutic target for HIV-related neuropathology. Springer International Publishing 2021-01-06 2021 /pmc/articles/PMC7786889/ /pubmed/33405206 http://dx.doi.org/10.1007/s13365-020-00927-z Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Mavian, Carla
Ramirez-Mata, Andrea S.
Dollar, James Jarad
Nolan, David J.
Cash, Melanie
White, Kevin
Rich, Shannan N.
Magalis, Brittany Rife
Marini, Simone
Prosperi, Mattia C. F.
Amador, David Moraga
Riva, Alberto
Williams, Kenneth C.
Salemi, Marco
Brain tissue transcriptomic analysis of SIV-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis and poly (ADP-ribose) polymerases (PARPs) as potential therapeutic targets
title Brain tissue transcriptomic analysis of SIV-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis and poly (ADP-ribose) polymerases (PARPs) as potential therapeutic targets
title_full Brain tissue transcriptomic analysis of SIV-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis and poly (ADP-ribose) polymerases (PARPs) as potential therapeutic targets
title_fullStr Brain tissue transcriptomic analysis of SIV-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis and poly (ADP-ribose) polymerases (PARPs) as potential therapeutic targets
title_full_unstemmed Brain tissue transcriptomic analysis of SIV-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis and poly (ADP-ribose) polymerases (PARPs) as potential therapeutic targets
title_short Brain tissue transcriptomic analysis of SIV-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis and poly (ADP-ribose) polymerases (PARPs) as potential therapeutic targets
title_sort brain tissue transcriptomic analysis of siv-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis and poly (adp-ribose) polymerases (parps) as potential therapeutic targets
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786889/
https://www.ncbi.nlm.nih.gov/pubmed/33405206
http://dx.doi.org/10.1007/s13365-020-00927-z
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