Blockade of beta adrenergic receptors protects the blood brain barrier and reduces systemic pathology caused by HIV-1 Nef protein.

Combination antiretroviral therapy (cART) targets viral replication, but early viral protein production by astrocytes may still occur and contribute to the progression of HIV-1 associated neurocognitive disorders and secondary complications seen in patients receiving cART. In prior work with our mod...

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Autores principales:	Jocelyn Rivera-Ortiz, Jessalyn Pla-Tenorio, Myrella L Cruz, Krystal Colon, Jaileene Perez-Morales, Julio A Rodriguez, Jorge Martinez-Sicari, Richard J Noel
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e5103326581c4054a8272c07c598e927
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spelling	oai:doaj.org-article:e5103326581c4054a8272c07c598e9272021-12-02T20:13:01ZBlockade of beta adrenergic receptors protects the blood brain barrier and reduces systemic pathology caused by HIV-1 Nef protein.1932-620310.1371/journal.pone.0259446https://doaj.org/article/e5103326581c4054a8272c07c598e9272021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0259446https://doaj.org/toc/1932-6203Combination antiretroviral therapy (cART) targets viral replication, but early viral protein production by astrocytes may still occur and contribute to the progression of HIV-1 associated neurocognitive disorders and secondary complications seen in patients receiving cART. In prior work with our model, astrocytic HIV-1 Nef expression exhibits neurotoxic effects leading to neurological damage, learning impairment, and immune upregulation that induces inflammation in the lungs and small intestine (SI). In this follow-up study, we focus on the sympathetic nervous system (SNS) as the important branch for peripheral inflammation resulting from astrocytic Nef expression. Male and female Sprague Dawley rats were infused with transfected astrocytes to produce Nef. The rats were divided in four groups: Nef, Nef + propranolol, propranolol and naïve. The beta-adrenergic blocker, propranolol, was administered for 3 consecutive days, starting one day prior to surgery. Two days after the surgery, the rats were sacrificed, and then blood, brain, small intestine (SI), and lung tissues were collected. Levels of IL-1β were higher in both male and female rats, and treatment with propranolol restored IL-1β to basal levels. We observed that Nef expression decreased staining of the tight junction protein claudin-5 in brain tissue while animals co-treated with propranolol restored claudin-5 expression. Lungs and SI of rats in the Nef group showed histological signs of damage including larger Peyer's Patches, increased tissue thickness, and infiltration of immune cells; these findings were abrogated by propranolol co-treatment. Results suggest that interruption of the beta adrenergic signaling reduces the peripheral organ inflammation caused after Nef expression in astrocytes of the brain.Jocelyn Rivera-OrtizJessalyn Pla-TenorioMyrella L CruzKrystal ColonJaileene Perez-MoralesJulio A RodriguezJorge Martinez-SicariRichard J NoelPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11, p e0259446 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jocelyn Rivera-Ortiz Jessalyn Pla-Tenorio Myrella L Cruz Krystal Colon Jaileene Perez-Morales Julio A Rodriguez Jorge Martinez-Sicari Richard J Noel Blockade of beta adrenergic receptors protects the blood brain barrier and reduces systemic pathology caused by HIV-1 Nef protein.
description	Combination antiretroviral therapy (cART) targets viral replication, but early viral protein production by astrocytes may still occur and contribute to the progression of HIV-1 associated neurocognitive disorders and secondary complications seen in patients receiving cART. In prior work with our model, astrocytic HIV-1 Nef expression exhibits neurotoxic effects leading to neurological damage, learning impairment, and immune upregulation that induces inflammation in the lungs and small intestine (SI). In this follow-up study, we focus on the sympathetic nervous system (SNS) as the important branch for peripheral inflammation resulting from astrocytic Nef expression. Male and female Sprague Dawley rats were infused with transfected astrocytes to produce Nef. The rats were divided in four groups: Nef, Nef + propranolol, propranolol and naïve. The beta-adrenergic blocker, propranolol, was administered for 3 consecutive days, starting one day prior to surgery. Two days after the surgery, the rats were sacrificed, and then blood, brain, small intestine (SI), and lung tissues were collected. Levels of IL-1β were higher in both male and female rats, and treatment with propranolol restored IL-1β to basal levels. We observed that Nef expression decreased staining of the tight junction protein claudin-5 in brain tissue while animals co-treated with propranolol restored claudin-5 expression. Lungs and SI of rats in the Nef group showed histological signs of damage including larger Peyer's Patches, increased tissue thickness, and infiltration of immune cells; these findings were abrogated by propranolol co-treatment. Results suggest that interruption of the beta adrenergic signaling reduces the peripheral organ inflammation caused after Nef expression in astrocytes of the brain.
format	article
author	Jocelyn Rivera-Ortiz Jessalyn Pla-Tenorio Myrella L Cruz Krystal Colon Jaileene Perez-Morales Julio A Rodriguez Jorge Martinez-Sicari Richard J Noel
author_facet	Jocelyn Rivera-Ortiz Jessalyn Pla-Tenorio Myrella L Cruz Krystal Colon Jaileene Perez-Morales Julio A Rodriguez Jorge Martinez-Sicari Richard J Noel
author_sort	Jocelyn Rivera-Ortiz
title	Blockade of beta adrenergic receptors protects the blood brain barrier and reduces systemic pathology caused by HIV-1 Nef protein.
title_short	Blockade of beta adrenergic receptors protects the blood brain barrier and reduces systemic pathology caused by HIV-1 Nef protein.
title_full	Blockade of beta adrenergic receptors protects the blood brain barrier and reduces systemic pathology caused by HIV-1 Nef protein.
title_fullStr	Blockade of beta adrenergic receptors protects the blood brain barrier and reduces systemic pathology caused by HIV-1 Nef protein.
title_full_unstemmed	Blockade of beta adrenergic receptors protects the blood brain barrier and reduces systemic pathology caused by HIV-1 Nef protein.
title_sort	blockade of beta adrenergic receptors protects the blood brain barrier and reduces systemic pathology caused by hiv-1 nef protein.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/e5103326581c4054a8272c07c598e927
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Blockade of beta adrenergic receptors protects the blood brain barrier and reduces systemic pathology caused by HIV-1 Nef protein.

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