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Vorinostat positively regulates synaptic plasticity genes expression and spine density in HIV infected neurons: role of nicotine in progression of HIV-associated neurocognitive disorder
BACKGROUND: HIV-associated neurocognitive disorder (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occurs in approximately 50% of HIV infected individuals. In the United States, the prevalence of cigarette smoking ranges from 35-70% in HIV-infected indivi...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4040511/ https://www.ncbi.nlm.nih.gov/pubmed/24886748 http://dx.doi.org/10.1186/1756-6606-7-37 |
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author | Atluri, Venkata Subba Rao Pilakka-Kanthikeel, Sudheesh Samikkannu, Thangavel Sagar, Vidya Kurapati, Kesava Rao Venkata Saxena, Shailendra K Yndart, Adriana Raymond, Andrea Ding, Hong Hernandez, Oscar Nair, Madhavan PN |
author_facet | Atluri, Venkata Subba Rao Pilakka-Kanthikeel, Sudheesh Samikkannu, Thangavel Sagar, Vidya Kurapati, Kesava Rao Venkata Saxena, Shailendra K Yndart, Adriana Raymond, Andrea Ding, Hong Hernandez, Oscar Nair, Madhavan PN |
author_sort | Atluri, Venkata Subba Rao |
collection | PubMed |
description | BACKGROUND: HIV-associated neurocognitive disorder (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occurs in approximately 50% of HIV infected individuals. In the United States, the prevalence of cigarette smoking ranges from 35-70% in HIV-infected individuals compared to 20% in general population. Cognitive impairment in heavy cigarette smokers has been well reported. However, the synergistic effects of nicotine and HIV infection and the underlying mechanisms in the development of HAND are unknown. RESULTS: In this study, we explored the role of nicotine in the progression of HAND using SK-N-MC, a neuronal cell line. SK-N-MC cells were infected with HIV-1 in the presence or absence of nicotine for 7 days. We observed significant increase in HIV infectivity in SK-N-MC treated with nicotine compared to untreated HIV-infected neuronal cells. HIV and nicotine synergize to significantly dysregulate the expression of synaptic plasticity genes and spine density; with a concomitant increase of HDAC2 levels in SK-N-MC cells. In addition, inhibition of HDAC2 up-regulation with the use of vorinostat resulted in HIV latency breakdown and recovery of synaptic plasticity genes expression and spine density in nicotine/HIV alone and in co-treated SK-N-MC cells. Furthermore, increased eIF2 alpha phosphorylation, which negatively regulates eukaryotic translational process, was observed in HIV alone and in co-treatment with nicotine compared to untreated control and nicotine alone treated SK-N-MC cells. CONCLUSIONS: These results suggest that nicotine and HIV synergize to negatively regulate the synaptic plasticity gene expression and spine density and this may contribute to the increased risk of HAND in HIV infected smokers. Apart from disrupting latency, vorinostat may be a useful therapeutic to inhibit the negative regulatory effects on synaptic plasticity in HIV infected nicotine abusers. |
format | Online Article Text |
id | pubmed-4040511 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-40405112014-06-03 Vorinostat positively regulates synaptic plasticity genes expression and spine density in HIV infected neurons: role of nicotine in progression of HIV-associated neurocognitive disorder Atluri, Venkata Subba Rao Pilakka-Kanthikeel, Sudheesh Samikkannu, Thangavel Sagar, Vidya Kurapati, Kesava Rao Venkata Saxena, Shailendra K Yndart, Adriana Raymond, Andrea Ding, Hong Hernandez, Oscar Nair, Madhavan PN Mol Brain Research BACKGROUND: HIV-associated neurocognitive disorder (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occurs in approximately 50% of HIV infected individuals. In the United States, the prevalence of cigarette smoking ranges from 35-70% in HIV-infected individuals compared to 20% in general population. Cognitive impairment in heavy cigarette smokers has been well reported. However, the synergistic effects of nicotine and HIV infection and the underlying mechanisms in the development of HAND are unknown. RESULTS: In this study, we explored the role of nicotine in the progression of HAND using SK-N-MC, a neuronal cell line. SK-N-MC cells were infected with HIV-1 in the presence or absence of nicotine for 7 days. We observed significant increase in HIV infectivity in SK-N-MC treated with nicotine compared to untreated HIV-infected neuronal cells. HIV and nicotine synergize to significantly dysregulate the expression of synaptic plasticity genes and spine density; with a concomitant increase of HDAC2 levels in SK-N-MC cells. In addition, inhibition of HDAC2 up-regulation with the use of vorinostat resulted in HIV latency breakdown and recovery of synaptic plasticity genes expression and spine density in nicotine/HIV alone and in co-treated SK-N-MC cells. Furthermore, increased eIF2 alpha phosphorylation, which negatively regulates eukaryotic translational process, was observed in HIV alone and in co-treatment with nicotine compared to untreated control and nicotine alone treated SK-N-MC cells. CONCLUSIONS: These results suggest that nicotine and HIV synergize to negatively regulate the synaptic plasticity gene expression and spine density and this may contribute to the increased risk of HAND in HIV infected smokers. Apart from disrupting latency, vorinostat may be a useful therapeutic to inhibit the negative regulatory effects on synaptic plasticity in HIV infected nicotine abusers. BioMed Central 2014-05-15 /pmc/articles/PMC4040511/ /pubmed/24886748 http://dx.doi.org/10.1186/1756-6606-7-37 Text en Copyright © 2014 Atluri et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Atluri, Venkata Subba Rao Pilakka-Kanthikeel, Sudheesh Samikkannu, Thangavel Sagar, Vidya Kurapati, Kesava Rao Venkata Saxena, Shailendra K Yndart, Adriana Raymond, Andrea Ding, Hong Hernandez, Oscar Nair, Madhavan PN Vorinostat positively regulates synaptic plasticity genes expression and spine density in HIV infected neurons: role of nicotine in progression of HIV-associated neurocognitive disorder |
title | Vorinostat positively regulates synaptic plasticity genes expression and spine density in HIV infected neurons: role of nicotine in progression of HIV-associated neurocognitive disorder |
title_full | Vorinostat positively regulates synaptic plasticity genes expression and spine density in HIV infected neurons: role of nicotine in progression of HIV-associated neurocognitive disorder |
title_fullStr | Vorinostat positively regulates synaptic plasticity genes expression and spine density in HIV infected neurons: role of nicotine in progression of HIV-associated neurocognitive disorder |
title_full_unstemmed | Vorinostat positively regulates synaptic plasticity genes expression and spine density in HIV infected neurons: role of nicotine in progression of HIV-associated neurocognitive disorder |
title_short | Vorinostat positively regulates synaptic plasticity genes expression and spine density in HIV infected neurons: role of nicotine in progression of HIV-associated neurocognitive disorder |
title_sort | vorinostat positively regulates synaptic plasticity genes expression and spine density in hiv infected neurons: role of nicotine in progression of hiv-associated neurocognitive disorder |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4040511/ https://www.ncbi.nlm.nih.gov/pubmed/24886748 http://dx.doi.org/10.1186/1756-6606-7-37 |
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