@article{ae880b8a678d48abaf7bc4100b19a571,
title = "Deprenyl reduces inflammation during acute SIV infection",
abstract = "In the era of antiretroviral therapy, inflammation is a central factor in numerous HIV-associated comorbidities, such as cardiovascular disease, cognitive impairment, and neuropsychiatric disorders. This highlights the value of developing therapeutics that both reduce HIV-associated inflammation and treat associated comorbidities. Previous research on monoamine oxidase inhibitors (MAOIs) suggests this class of drugs has anti-inflammatory properties in addition to neuropsychiatric effects. Therefore, we examined the impact of deprenyl, an MAOI, on SIV-associated inflammation during acute SIV infection using the rhesus macaque model of HIV infection. Our results show deprenyl decreased both peripheral and CNS inflammation but had no effect on viral load in either the periphery or CNS. These data show that the MAOI deprenyl may have broad anti-inflammatory effects when given during the acute stage of SIV infection, suggesting more research into the anti-inflammatory effects of this drug could result in a beneficial adjuvant for antiretroviral therapy.",
keywords = "Biological sciences, Immunology, Microbiology",
author = "Emanuel, {K. M.} and K. Runner and Brodnik, {Z. D.} and Morsey, {B. M.} and Lamberty, {B. G.} and Johnson, {H. S.} and A. Acharya and Byrareddy, {S. N.} and Espa{\~n}a, {R. A.} and Fox, {H. S.} and Gaskill, {P. J.}",
note = "Funding Information: We would like to thank Gaskill lab members Samyuktha Manikandan, Heidi Joyce, Krisna Mompho, and Breana Channer for helping with image processing. We would like to give a special thanks to Dr. Holly Moore, who provided critical guidance on the preservation of monoamines in tissue. We would also like to thank all the members of Gaskill and Fox labs for ongoing discussions that helped to formulate and synthesize the concepts discussed in this paper, as well as the DNA Sequencing (DNAS) and Flow Cytometry Research (FCR) at UNMC for assistance. This work was supported by the National Institutes of Health ( R01DA039005 and R21DA049227 to PJG, R01DA04316 to HSF and SNB, R01DA043258 and P30MH062261 to HSF, R01DA031900 to RAE) and the W. W. Smith Charitable Trust ( A2003 to PJG). The DNA Sequencing (DNAS) and Flow Cytometry Research (FCR) receive partial support from the NIH National Institute of General Medical Sciences INBRE P20GM103427 (DNAS), and COBRE P30GM110768 (DNAS) grants, NIH National Cancer Institute Cancer Support Grant P30CA036727 (FCR), and the Nebraska Research Initiative (FCR) . Major instrumentation has been provided by the UNMC Office of the Vice Chancellor for Research, the University of Nebraska Foundation of N, the Nebraska Banker{\textquoteright}s Fund, and by the NIH NCRR / NIGMS Shared Instrument Program. Funding Information: We would like to thank Gaskill lab members Samyuktha Manikandan, Heidi Joyce, Krisna Mompho, and Breana Channer for helping with image processing. We would like to give a special thanks to Dr. Holly Moore, who provided critical guidance on the preservation of monoamines in tissue. We would also like to thank all the members of Gaskill and Fox labs for ongoing discussions that helped to formulate and synthesize the concepts discussed in this paper, as well as the DNA Sequencing (DNAS) and Flow Cytometry Research (FCR) at UNMC for assistance. This work was supported by the National Institutes of Health (R01DA039005 and R21DA049227 to PJG, R01DA04316 to HSF and SNB, R01DA043258 and P30MH062261 to HSF, R01DA031900 to RAE) and the W. W. Smith Charitable Trust (A2003 to PJG). The DNA Sequencing (DNAS) and Flow Cytometry Research (FCR) receive partial support from the NIH National Institute of General Medical Sciences INBRE P20GM103427 (DNAS), and COBRE P30GM110768 (DNAS) grants, NIH National Cancer Institute Cancer Support Grant P30CA036727 (FCR), and the Nebraska Research Initiative (FCR). Major instrumentation has been provided by the UNMC Office of the Vice Chancellor for Research, the University of Nebraska Foundation of N, the Nebraska Banker's Fund, and by the NIH NCRR/NIGMS Shared Instrument Program. PJG conceptualized the project; HSF and PJG designed the experiments; BM, BGL, and HSF maintained, treated, and processed the rhesus macaques; KR managed data and sample exchange between UNMC and Drexel; KME, KR, HSJ, and HSF performed and processed the immunohistochemistry and RNAscope in situ hybridization; KME isolated RNA for viral load and NanoString analysis; BM performed the flow cytometry; AA and SNB performed the analysis of plasma and tissue viral load; ZDB and RAE performed the HPLC analysis of CNS monoamines; HSF and PJG analyzed the data; PJG wrote the original manuscript; KME, ZDB, KR, BM, HSF, and PJG edited the manuscript and all authors edited and approved of the final submission. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = may,
day = "20",
doi = "10.1016/j.isci.2022.104207",
language = "English (US)",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "5",
}