Journal article
Blockade of beta adrenergic receptors protects the blood brain barrier and reduces systemic pathology caused by HIV-1 Nef protein
PloS one, v 16(11), pp e0259446-e0259446
16 Nov 2021
PMID: 34784367
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 naive. 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-1 beta were higher in both male and female rats, and treatment with propranolol restored IL-1 beta 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.
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Details
- Title
- Blockade of beta adrenergic receptors protects the blood brain barrier and reduces systemic pathology caused by HIV-1 Nef protein
- Creators
- Jocelyn Rivera-Ortiz - Wistar Inst Anat & Biol, HIV Immunopathogenesis Lab 1, 3601 Spruce St, Philadelphia, PA 19104 USAJessalyn Pla-Tenorio - Ponce Health Sciences UniversityMyrella L. Cruz - Ponce Health Sciences UniversityKrystal Colon - The Wistar InstituteJaileene Perez-Morales - Ponce Health Sciences UniversityJulio A. Rodriguez - Cooper University HospitalJorge Martinez-Sicari - Ponce Health Sciences UniversityRichard J. Noel - Ponce Health Sciences University
- Publication Details
- PloS one, v 16(11), pp e0259446-e0259446
- Publisher
- Public Library Science
- Number of pages
- 16
- Grant note
- 2U54CA163071-06 / NIHNCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Behavioral Research and Integrative Neuroscience Core Molecular and Genomics Core GM106970; DA026722; MD007579; 5R25GM08240611 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000755277300011
- Scopus ID
- 2-s2.0-85119418388
- Other Identifier
- 991021961009504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences