Dopamine, Immunity, and Disease

Pharmacological Reviews, Journal Year: 2022, Volume and Issue: 75(1), P. 62 - 158

Published: Dec. 8, 2022

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 peripheral organs, such as blood pressure, renal activity, intestinal motility. Beyond these functions, growing body of evidence indicates that an important immunoregulatory factor. Most types immune cells express receptors other dopaminergic proteins, take up, produce, store, and/or release dopamine, suggesting immunomodulation for function. Targeting pathways could be promising avenue the treatment inflammation disease, but despite increasing research this area, data on specific effects disease remain inconsistent poorly understood. Therefore, review integrates current knowledge role cell function inflammatory signaling across systems. We discuss understanding regulation CNS tissues, highlighting diseases Parkinson’s several neuropsychiatric conditions, neurologic human immunodeficiency virus, bowel rheumatoid arthritis, others. Careful consideration given to influence experimental design results, we note number areas need further research. Overall, our immunology at cellular, tissue, level prompts development therapeutics strategies targeted toward ameliorating through immunity.

Significance Statement

Canonically, recognized involved cognition, reward. However, acts modulator periphery. This comprehensively assesses pathogenesis cellular tissue level. will provide broad access information fields, identify investigation, drive therapeutic strategies.

Language: Английский

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Comparative Analysis of Neuropsychiatric Adverse Reactions Associated with Remdesivir and Nirmatrelvir/Ritonavir in COVID-19 Treatment: Insights from EudraVigilance Data

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(6), P. 1886 - 1886

Published: March 11, 2025

Remdesivir (RDV) and nirmatrelvir/ritonavir (NMVr) are among the most widely used antivirals in treatment of COVID-19, aiming to reduce disease severity progression. Adverse neuropsychiatric effects, such as anxiety, sleep disturbances, movement disorders, have emerged significant concerns associated with these treatments. To better understand safety profiles RDV NMVr, this study performs a pharmacovigilance analysis individual case reports (ICSRs) from EudraVigilance (EV) database. Objectives: This evaluates risk adverse events NMVr. Comparisons other antiviral drugs, including darunavir, sofosbuvir, ribavirin, tenofovir, ritonavir, sotrovimab, also performed develop comprehensive understanding profiles. Methods: A retrospective ICSRs submitted EV until 7 July 2024, data extraction on 12 was conducted. Demographic characteristics (age, sex, geographic region, reporter type) were included descriptive analysis. Disproportionality using reporting odds ratio (ROR) 95% confidence intervals (CI) compare drug reaction (ADRs) frequencies across 27 system organ classes (SOCs), emphasis “Nervous disorders” “Psychiatric disorders. Results: The total number significantly higher for NMVr (n = 8078) compared 3934). Nervous disorders accounted 3.07% 17.31% reports, while psychiatric represented 0.92% ADRs reported 60) 3.61% 672). On hand, showed lower frequency headache (ROR: 0.1057; CI: 0.0676–0.1653). Conclusions: presents than RDV, underscoring need enhanced monitoring, particularly patients preexisting central nervous (CNS) conditions. These findings contribute optimizing informing clinical decision making.

Language: Английский

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Systemic inflammation is associated with depressive symptoms differentially by sex and race: a longitudinal study of urban adults

Molecular Psychiatry, Journal Year: 2019, Volume and Issue: 25(6), P. 1286 - 1300

Published: April 24, 2019

Systemic inflammation may influence trajectories of depressive symptoms over time, perhaps differentially by sex and race. Inflammatory markers the Center for Epidemiologic Studies-Depression scale [total score: CES-Dtotal four distinctive domains: somatic complaints, depressed affect, positive affect interpersonal problems] were examined among African-American (AA) White urban adults participating in Healthy Aging Neighborhoods Diversity across Life Span (HANDLS) study [2004-2013, Agebase:30-64 y, mean ± SD follow-up time: 4.64 0.93 N = 150 (with cytokine data) to 1,767 other inflammatory markers)]. Findings suggest that serum concentrations high-sensitivity C-reactive protein (hsCRP), z-inflammation composite score [ICS, combining elevated hsCRP ESR with low albumin iron], interleukin (IL) 1β positively associated ΔCES-Dtotal (Δ: annual rate increase) Whites only. IL-12 was directly related men AA. The race-specific associations hsCRP, ICS, IL-1β sex-specific association replicated "depressed affect" domain. Similarly, men, lower higher ICS linked baseline "somatic complaints". IL-10 AA inversely Δ"positive affect", while "interpersonal problems" cross-sectionally IL-6 Whites. Finally, incident "elevated symptoms" (EDS: ≥ 16) (HR 1.28, 95% CI: 1.04-1.56, P 0.017). Overall, systemic increased time at baseline, race groups. More longitudinal research is needed replicate our findings.

Language: Английский

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Role of Macrophage Dopamine Receptors in Mediating Cytokine Production: Implications for Neuroinflammation in the Context of HIV-Associated Neurocognitive Disorders

Journal of Neuroimmune Pharmacology, Journal Year: 2018, Volume and Issue: 14(1), P. 134 - 156

Published: Dec. 5, 2018

Language: Английский

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Dopamine activates NF-κB and primes the NLRP3 inflammasome in primary human macrophages

Brain Behavior & Immunity - Health, Journal Year: 2019, Volume and Issue: 2, P. 100030 - 100030

Published: Dec. 31, 2019

Induction of innate immune genes in the brain is thought to be a major factor development addiction substances abuse. As component system brain, aberrant activation myeloid cells such as macrophages and microglia due substance use may mediate neuroinflammation contribute addiction. All addictive drugs modulate dopaminergic our previous studies have identified dopamine pro-inflammatory modulator macrophage function. However, mechanism that mediates this effect currently unknown. Inflammatory induction cytokine production often mediated by transcription NF-κB, prior shown can NF-κB activity T-cells other non-immune cell lines. Here we demonstrated activate primary human macrophages, resulting its downstream targets including NLRP3 inflammasome inflammatory IL-1β. These data also indicate primes but does not macrophages. Activation was required for dopamine-mediated increases IL-1β, an inhibitor able abrogate effects on these cytokines. Connecting increase extracellular inflammation suggests specific intracellular could used ameliorate impact neuroinflammatory conditions associated with

Language: Английский

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HIV Neuropathogenesis in the Presence of a Disrupted Dopamine System

Journal of Neuroimmune Pharmacology, Journal Year: 2020, Volume and Issue: 15(4), P. 729 - 742

Published: June 6, 2020

Language: Английский

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Co-receptor signaling in the pathogenesis of neuroHIV

Retrovirology, Journal Year: 2021, Volume and Issue: 18(1)

Published: Aug. 24, 2021

Abstract The HIV co-receptors, CCR5 and CXCR4, are necessary for entry into target cells, interacting with the envelope protein, gp120, to initiate several signaling cascades thought be important process. Co-receptor may also promote development of neuroHIV by contributing both persistent neuroinflammation indirect neurotoxicity. But despite critical importance CXCR4 pathogenesis, there is only one therapeutic (the inhibitor Maraviroc) that targets these receptors. Moreover, our understanding co-receptor in specific context relatively poor. Research has largely stalled past decade, possibly owing complexity functions mediated Examining many pathways triggered activation been challenging due lack molecular tools targeting proteins involved wide array model systems used across experiments. Studies examining impact on neuropathogenesis often show multiple overlapping similar stimuli, leading contradictory data effects activation. To address this, we will broadly review infection neuropathogenesis, examine different functions, then discuss differences between induced cognate ligands. We assess focusing neuroinflammation. explore how use substances abuse, which highly prevalent people living HIV, can exacerbate neuropathogenic signaling. Finally, current state therapeutics highlighting challenges field faced areas research would yield most benefit infection. This discussion provide a comprehensive overview what known remains explored regard infection, emphasize potential value co-receptors as future development.

Language: Английский

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Acute stimulation of PBMCs drives switch from dopamine-induced anti- to proinflammatory phenotype of monocytes only in women

Biology of Sex Differences, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 3, 2025

Language: Английский

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Dopamine-driven increase in IL-1β in myeloid cells is mediated by differential dopamine receptor expression and exacerbated by HIV

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: March 23, 2025

The catecholamine neurotransmitter dopamine is classically known for regulation of central nervous system (CNS) functions such as reward, movement, and cognition. Increasing evidence also indicates that regulates critical in peripheral organs an important immunoregulatory factor. We have previously shown increases NF-κB activity, inflammasome activation, the production inflammatory cytokines IL-1β human macrophages. As myeloid lineage cells are to initiation resolution acute responses, dopamine-mediated dysregulation these could both impair innate immune response exacerbate chronic inflammation. However, exact pathways by which drives inflammation not well defined, studies rodent systems indicate can impact mediators through D1-like receptors (DRD1, DRD5) D2-like (DRD2, DRD3, DRD4). Therefore, we hypothesized regulated ratio different activated. Our data primary monocyte-derived macrophages (hMDM) DRD1 expression necessary IL-1β, changes DRD2 other alter magnitude increase IL-1β. Mature hMDM a high receptor ratio, relative monocytes blood mononuclear (PBMCs). further confirm microglia cell lines promotes dopamine-induced gene protein using pharmacological inhibition or overexpression receptors. RNA-sequencing dopamine-treated shows genes encoding signaling pathways, neurotransmission increased with treatment. Finally, HIV example disease substantively worsened comorbid substance use disorders (SUDs) dopaminergic signaling, show effects on activation presence microglia. These suggest addictive substances dopamine-modulating therapeutics dysregulate neuroimmunological conditions like HIV. Thus, detailed understanding inflammation, particular regulating will be effectively tailor medication regimens.

Language: Английский

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Epidemiological and spatiotemporal analysis of elderly HIV-1/AIDS patients in Ningxia, China, from 2018 to 2023

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 23, 2025

Language: Английский

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