Deprenyl reduces inflammation during acute SIV infection

Emanuel, Katy; Runner, Kaitlyn; Brodnik, Zachary D.; Morsey, Brenda; Lamberty, B.G.H.; Johnson, Hannah S.; Acharya, Arpan; Byrareddy, Siddappa N.; España, Rodrigo A.; Fox, Howard S.; Gaskill, Peter J.

doi:10.1016/j.isci.2022.104207

Cited by 7 publications

(9 citation statements)

References 150 publications

(196 reference statements)

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“…In contrast to the other studies using selegiline, recent data show that selegiline treatment of macaques prior to and during acute (1–2 weeks postinfection) SIV infection reduced inflammatory and antiviral gene expression in the CNS, also reducing markers of peripheral inflammation. This correlates with earlier discussions noting that the impact of dopamine on inflammation changes depending on the environment and suggests that dopamine mediated impairment in the inflammatory and antiviral response early in infection could predispose these animals to a more robust disease course ( Emanuel et al, 2022 ). In SIV-infected rhesus macaques that were treated with methamphetamine during chronic infection, they showed increased viral load in the caudate and enhanced expression of inflammatory factors in CNS myeloid cells ( Marcondes et al, 2010 ; Najera et al, 2016 ), although chronic cocaine administration in pig-tailed macaques did not alter neuroinflammation and slightly reduced CSF viral RNA levels late in infection ( Weed et al, 2012 ).…”

Section: Regional and Disease-specific Effects Of Dopaminesupporting

confidence: 88%

“…This effect was also seen in the striatum of HIV-infected, encephalitic brains ( Meulendyke et al, 2014 ) and suggests that accelerated dopamine breakdown could produce ROS to increase myeloid cell activation and drive neuroinflammation. However, this finding conflicts with other studies showing that the inhibition of MAO-B during peak viremia increased myeloid activation, neuroinflammation and viral load ( Czub et al, 2001 , 2004 ), as well as recent data showing that inhibiting MAO during acute infection was anti-inflammatory ( Emanuel et al, 2022 ). These data also conflict with clinical trials testing the selegiline transdermal system to treat cognitive impairment in PLWH.…”

Section: Regional and Disease-specific Effects Of Dopaminecontrasting

confidence: 75%

“…Oxidation can also affect dopamine metabolites and may be more pronounced in certain regions, generating artificial distortions in dopamine:dopamine metabolite ratios and regional differences in dopamine levels and metabolism ( Sloviter and Connor, 1977 ; Graham et al, 1978 ; Spokes and Koch, 1978 ; Kontur et al, 1994 ; Sun et al, 2018 ). Rapid tissue processing, processing under anoxic conditions ( Morelli et al, 2011 ; Emanuel et al, 2022 ), and isolation and storage at colder temperatures can prevent oxidation and may provide a more accurate measurement of tissue dopamine levels.…”

Section: Considerations and Caveats Regarding The Study Of Dopaminerg...mentioning

confidence: 99%

“…Additionally, a recent study from the Translational Methamphetamine AIDS Research Center cohort showed slight, nonsignificant increases in dopamine and HVA in the CSF of chronically infected PLWH on ART ( Saloner et al, 2020 ). A separate study in rhesus macaques showed that SIV infection significantly increases dopamine, DOPAC, serotonin, and HVA levels in the frontal cortex, and dopamine levels in the caudate during acute infection ( Emanuel et al, 2022 ). The conflicting results of these studies suggest that the impact of HIV on CNS dopamine is regulated by many factors, including HIV and viral proteins, disease stage, ART use, and substance use.…”

Section: Regional and Disease-specific Effects Of Dopaminementioning

confidence: 99%

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Dopamine, Immunity, and Disease

et al. 2022

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The neurotransmitter dopamine is a key factor in central nervous system (CNS) function, regulating many processes including reward, movement, and cognition. Dopamine also regulates critical functions in peripheral organs, such as blood pressure, renal activity, and intestinal motility. Beyond these functions, a growing body of evidence indicates that dopamine is an important immunoregulatory factor. Most types of immune cells express dopamine receptors and other dopaminergic proteins, and many immune cells take up, produce, store, and/or release dopamine, suggesting that dopaminergic immunomodulation is important for immune function. Targeting these pathways could be a promising avenue for the treatment of inflammation and disease, but despite increasing research in this area, data on the specific effects of dopamine on many immune cells and disease processes remain inconsistent and poorly understood. Therefore, this review integrates the current knowledge of the role of dopamine in immune cell function and inflammatory signaling across systems. We also discuss the current understanding of dopaminergic regulation of immune signaling in the CNS and peripheral tissues, highlighting the role of dopaminergic immunomodulation in diseases such as Parkinson’s disease, several neuropsychiatric conditions, neurologic human immunodeficiency virus, inflammatory bowel disease, rheumatoid arthritis, and others. Careful consideration is given to the influence of experimental design on results, and we note a number of areas in need of further research. Overall, this review integrates our knowledge of dopaminergic immunology at the cellular, tissue, and disease level and prompts the development of therapeutics and strategies targeted toward ameliorating disease through dopaminergic regulation of immunity. Significance Statement Canonically, dopamine is recognized as a neurotransmitter involved in the regulation of movement, cognition, and reward. However, dopamine also acts as an immune modulator in the central nervous system and periphery. This review comprehensively assesses the current knowledge of dopaminergic immunomodulation and the role of dopamine in disease pathogenesis at the cellular and tissue level. This will provide broad access to this information across fields, identify areas in need of further investigation, and drive the development of dopaminergic therapeutic strategies.

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Section: Regional and Disease-specific Effects Of Dopaminesupporting

confidence: 88%

Section: Regional and Disease-specific Effects Of Dopaminecontrasting

confidence: 75%

Section: Considerations and Caveats Regarding The Study Of Dopaminerg...mentioning

confidence: 99%

Section: Regional and Disease-specific Effects Of Dopaminementioning

confidence: 99%

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Dopamine, Immunity, and Disease

et al. 2022

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“…Plasma, collected in EDTA-anticoagulated blood, was separated within an hour of collection and stored frozen at -80° C. Samples were sent to Myriad RBM (Austin, TX), a CLIA-certified lab, for multiplexed biomarker assay using the Human v2.0 Multianalyte profile (MAP) immunoassay. We previously reported the normal range for the 46 analytes that can be detected in rhesus macaques ( 59 ).…”

Section: Methodsmentioning

confidence: 99%

Morphine suppresses peripheral responses and transforms brain myeloid gene expression to favor neuropathogenesis in SIV infection

et al. 2022

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The twin pandemics of opioid abuse and HIV infection can have devastating effects on physiological systems, including on the brain. Our previous work found that morphine increased the viral reservoir in the brains of treated SIV-infected macaques. In this study, we investigated the interaction of morphine and SIV to identify novel host-specific targets using a multimodal approach. We probed systemic parameters and performed single-cell examination of the targets for infection in the brain, microglia and macrophages. Morphine treatment created an immunosuppressive environment, blunting initial responses to infection, which persisted during antiretroviral treatment. Antiretroviral drug concentrations and penetration into the cerebrospinal fluid and brain were unchanged by morphine treatment. Interestingly, the transcriptional signature of both microglia and brain macrophages was transformed to one of a neurodegenerative phenotype. Notably, the expression of osteopontin, a pleiotropic cytokine, was significantly elevated in microglia. This was especially notable in the white matter, which is also dually affected by HIV and opioids. Increased osteopontin expression was linked to numerous HIV neuropathogenic mechanisms, including those that can maintain a viral reservoir. The opioid morphine is detrimental to SIV/HIV infection, especially in the brain.

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Virus infection participates in the occurrence and development of human diseases through monoamine oxidase

Sun

Wen

Luo

2023

Reviews in Medical Virology

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Monoamine oxidase (MAO) is a membrane‐bound mitochondrial enzyme that maintains the steady state of neurotransmitters and other biogenic amines in biological systems through catalytic oxidation and deamination. MAO dysfunction is closely related to human neurological and psychiatric diseases and cancers. However, little is known about the relationship between MAO and viral infections in humans. This review summarises current research on how viral infections participate in the occurrence and development of human diseases through MAO. The viruses discussed in this review include hepatitis C virus, dengue virus, severe acute respiratory syndrome coronavirus 2, human immunodeficiency virus, Japanese encephalitis virus, Epstein‐Barr virus, and human papillomavirus. This review also describes the effects of MAO inhibitors such as phenelzine, clorgyline, selegiline, M‐30, and isatin on viral infectious diseases. This information will not only help us to better understand the role of MAO in the pathogenesis of viruses but will also provide new insights into the treatment and diagnosis of these viral diseases.

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Deprenyl reduces inflammation during acute SIV infection

Cited by 7 publications

References 150 publications

Dopamine, Immunity, and Disease

Dopamine, Immunity, and Disease

Morphine suppresses peripheral responses and transforms brain myeloid gene expression to favor neuropathogenesis in SIV infection

Virus infection participates in the occurrence and development of human diseases through monoamine oxidase

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