Development of TIMP1 magnetic nanoformulation for regulation of synaptic plasticity in HIV-1 infection

Venkata Subba Rao Atluri* Rahul Dev Jayant* Sudheesh Pilakka-Kanthikeel, Gabriella Garcia, Thangavel Samikkannu, Adriana Yndart, Ajeet Kaushik, Madhavan Nair Center for Personalized Nanomedicine, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami...

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Autores principales:	Atluri VSR, Jayant RD, Pilakka-Kanthikeel S, Garcia G, Samikkannu T, Yndart A, Kaushik A, Nair M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	HIV Neurocognitive disorders TIMP1 Magnetic nanoparticles Blood brain barrier Neuroprotection. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/20d4f406a3aa4b04b10edda7c0c0c5ac
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spelling	oai:doaj.org-article:20d4f406a3aa4b04b10edda7c0c0c5ac2021-12-02T00:46:39ZDevelopment of TIMP1 magnetic nanoformulation for regulation of synaptic plasticity in HIV-1 infection1178-2013https://doaj.org/article/20d4f406a3aa4b04b10edda7c0c0c5ac2016-08-01T00:00:00Zhttps://www.dovepress.com/development-of-timp1-magnetic-nanoformulation-for-regulation-of-synapt-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Venkata Subba Rao Atluri* Rahul Dev Jayant* Sudheesh Pilakka-Kanthikeel, Gabriella Garcia, Thangavel Samikkannu, Adriana Yndart, Ajeet Kaushik, Madhavan Nair Center for Personalized Nanomedicine, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA *These authors contributed equally to this work Abstract: Although the introduction of antiretroviral therapy has reduced the prevalence of severe forms of neurocognitive disorders, human immunodeficiency virus (HIV)-1-associated neurocognitive disorders were observed in 50% of HIV-infected patients globally. The blood–brain barrier is known to be impermeable to most of antiretroviral drugs. Successful delivery of antiretroviral drugs into the brain may induce an inflammatory response, which may further induce neurotoxicity. Therefore, alternate options to antiretroviral drugs for decreasing the HIV infection and neurotoxicity may help in reducing neurocognitive impairments observed in HIV-infected patients. In this study, we explored the role of magnetic nanoparticle (MNP)-bound tissue inhibitor of metalloproteinase-1 (TIMP1) protein in reducing HIV infection levels, oxidative stress, and recovering spine density in HIV-infected SK-N-MC neuroblastoma cells. We did not observe any neuronal cytotoxicity with either the free TIMP1 or MNP-bound TIMP1 used in our study. We observed significantly reduced HIV infection in both solution phase and in MNP-bound TIMP1-exposed neuronal cells. Furthermore, we also observed significantly reduced reactive oxygen species production in both the test groups compared to the neuronal cells infected with HIV alone. To observe the effect of both soluble-phase TIMP1 and MNP-bound TIMP1 on spine density in HIV-infected neuronal cells, confocal microscopy was used. We observed significant recovery of spine density in both the test groups when compared to the cells infected with HIV alone, indicting the neuroprotective effect of TIMP1. Therefore, our results suggest that the MNP-bound TIMP1 delivery method across the blood–brain barrier can be used for reducing HIV infectivity in brain tissue and neuronal toxicity in HIV-infected patients. Keywords: HIV, neurocognitive disorders, TIMP1, magnetic nanoparticles, blood–brain barrier, neuroprotectionAtluri VSRJayant RDPilakka-Kanthikeel SGarcia GSamikkannu TYndart AKaushik ANair MDove Medical PressarticleHIVNeurocognitive disordersTIMP1Magnetic nanoparticlesBlood brain barrierNeuroprotection.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 4287-4298 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIV Neurocognitive disorders TIMP1 Magnetic nanoparticles Blood brain barrier Neuroprotection. Medicine (General) R5-920
spellingShingle	HIV Neurocognitive disorders TIMP1 Magnetic nanoparticles Blood brain barrier Neuroprotection. Medicine (General) R5-920 Atluri VSR Jayant RD Pilakka-Kanthikeel S Garcia G Samikkannu T Yndart A Kaushik A Nair M Development of TIMP1 magnetic nanoformulation for regulation of synaptic plasticity in HIV-1 infection
description	Venkata Subba Rao Atluri* Rahul Dev Jayant* Sudheesh Pilakka-Kanthikeel, Gabriella Garcia, Thangavel Samikkannu, Adriana Yndart, Ajeet Kaushik, Madhavan Nair Center for Personalized Nanomedicine, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA *These authors contributed equally to this work Abstract: Although the introduction of antiretroviral therapy has reduced the prevalence of severe forms of neurocognitive disorders, human immunodeficiency virus (HIV)-1-associated neurocognitive disorders were observed in 50% of HIV-infected patients globally. The blood–brain barrier is known to be impermeable to most of antiretroviral drugs. Successful delivery of antiretroviral drugs into the brain may induce an inflammatory response, which may further induce neurotoxicity. Therefore, alternate options to antiretroviral drugs for decreasing the HIV infection and neurotoxicity may help in reducing neurocognitive impairments observed in HIV-infected patients. In this study, we explored the role of magnetic nanoparticle (MNP)-bound tissue inhibitor of metalloproteinase-1 (TIMP1) protein in reducing HIV infection levels, oxidative stress, and recovering spine density in HIV-infected SK-N-MC neuroblastoma cells. We did not observe any neuronal cytotoxicity with either the free TIMP1 or MNP-bound TIMP1 used in our study. We observed significantly reduced HIV infection in both solution phase and in MNP-bound TIMP1-exposed neuronal cells. Furthermore, we also observed significantly reduced reactive oxygen species production in both the test groups compared to the neuronal cells infected with HIV alone. To observe the effect of both soluble-phase TIMP1 and MNP-bound TIMP1 on spine density in HIV-infected neuronal cells, confocal microscopy was used. We observed significant recovery of spine density in both the test groups when compared to the cells infected with HIV alone, indicting the neuroprotective effect of TIMP1. Therefore, our results suggest that the MNP-bound TIMP1 delivery method across the blood–brain barrier can be used for reducing HIV infectivity in brain tissue and neuronal toxicity in HIV-infected patients. Keywords: HIV, neurocognitive disorders, TIMP1, magnetic nanoparticles, blood–brain barrier, neuroprotection
format	article
author	Atluri VSR Jayant RD Pilakka-Kanthikeel S Garcia G Samikkannu T Yndart A Kaushik A Nair M
author_facet	Atluri VSR Jayant RD Pilakka-Kanthikeel S Garcia G Samikkannu T Yndart A Kaushik A Nair M
author_sort	Atluri VSR
title	Development of TIMP1 magnetic nanoformulation for regulation of synaptic plasticity in HIV-1 infection
title_short	Development of TIMP1 magnetic nanoformulation for regulation of synaptic plasticity in HIV-1 infection
title_full	Development of TIMP1 magnetic nanoformulation for regulation of synaptic plasticity in HIV-1 infection
title_fullStr	Development of TIMP1 magnetic nanoformulation for regulation of synaptic plasticity in HIV-1 infection
title_full_unstemmed	Development of TIMP1 magnetic nanoformulation for regulation of synaptic plasticity in HIV-1 infection
title_sort	development of timp1 magnetic nanoformulation for regulation of synaptic plasticity in hiv-1 infection
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/20d4f406a3aa4b04b10edda7c0c0c5ac
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Development of TIMP1 magnetic nanoformulation for regulation of synaptic plasticity in HIV-1 infection

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