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

---

The systemic immune response in Parkinson’s disease: focus on the peripheral immune component

Trends in Neurosciences, Journal Year: 2023, Volume and Issue: 46(10), P. 863 - 878

Published: Aug. 17, 2023

Language: Английский

---

DAT and TH expression marks human Parkinson’s disease in peripheral immune cells

npj Parkinson s Disease, Journal Year: 2022, Volume and Issue: 8(1)

Published: June 7, 2022

Parkinson's disease (PD) is marked by a loss of dopamine neurons, decreased transporter (DAT) and tyrosine hydroxylase (TH) expression. However, this validation approach cannot be used for diagnostic, drug effectiveness or investigational purposes in human patients because midbrain tissue accessible postmortem. PD pathology affects both the central nervous peripheral immune systems. Therefore, we immunophenotyped blood samples presence myeloid derived suppressor cells (MDSCs) discovered that DAT

Language: Английский

---

Dopamine and norepinephrine are embracing their immune side and so should we

Current Opinion in Neurobiology, Journal Year: 2022, Volume and Issue: 77, P. 102626 - 102626

Published: Sept. 1, 2022

Language: Английский

---

Substance P promotes epidural fibrosis via induction of type 2 macrophages

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 18(10), P. 2252 - 2252

Published: Jan. 1, 2023

In response to spinal surgery, neurons secrete a large amount of substance P into the epidural area. Substance is involved in macrophage differentiation and fibrotic disease. However, specific roles mechanisms fibrosis remain unclear. this study, we established mouse model L1-L3 laminectomy found that dorsal root ganglion macrophages infiltrating wound area released sphingolipids. vitro experiments revealed type 1 secreted P, which promoted towards 2 phenotype. High-throughput mRNA-seq analysis sphingolipid metabolic pathway may be regulation by P. Specifically, sphingomyelin synthase 2, component pathway, M2 P-treated macrophages, while treating with LY93, inhibitor, suppressed differentiation. addition, formation neutrophil extracellular traps, further boosted Blocking neurokinin receptor inhibitor RP67580 decreased number after surgery alleviated fibrosis, as evidenced fibronectin, α-smooth muscle actin, collagen I scar tissue. These results demonstrated promotes via traps. findings provide novel strategy for treatment fibrosis.

Language: Английский

---

The complex role of inflammation and gliotransmitters in Parkinson's disease

Neurobiology of Disease, Journal Year: 2022, Volume and Issue: 176, P. 105940 - 105940

Published: Dec. 5, 2022

Our understanding of the role innate and adaptive immune cell function in brain health how it goes awry during aging neurodegenerative diseases is still its infancy. Inflammation immunological dysfunction are common components Parkinson's disease (PD), both terms motor non-motor PD. In recent decades, antiquated notion that central nervous system (CNS) states an immune-privileged organ, has been debunked. The landscape CNS influences peripheral systems, changes can alter disease. Identifying inflammatory pathways compromise neuronal survival critical designing innovative effective strategies to limit their untoward effects on health.

Language: Английский

---

Who Knew? Dopamine Transporter Activity Is Critical in Innate and Adaptive Immune Responses

Cells, Journal Year: 2023, Volume and Issue: 12(2), P. 269 - 269

Published: Jan. 10, 2023

The dopamine transporter (DAT) regulates the dimension and duration of transmission. DAT expression, its trafficking, protein–protein interactions, activity are conventionally studied in CNS within context neurological diseases such as Parkinson’s Diseases neuropsychiatric drug addiction, attention deficit hyperactivity autism. However, is also expressed at plasma membrane peripheral immune cells monocytes, macrophages, T-cells, B-cells. via an autocrine/paracrine signaling loop macrophage responses to stimulation. In a recent study, we identified immunosuppressive function for DAT, where blockade enhanced LPS-mediated production IL-6, TNF-α, mitochondrial superoxide levels, demonstrating that responses. current tested hypothesis knockout mice, innate adaptive immunity perturbed. We found genetic deletion (DAT−/−) results exaggerated baseline inflammatory phenotype circulating myeloid cells. peritoneal macrophages obtained from DAT−/− increased MHC-II expression phagocytic response LPS-induced stimulation, suppressed T-cell populations following systemic endotoxemia memory B cell expansion. norepinephrine levels spleen thymus, but not serum. These findings conjunction with hypoplasia, splenic cells, elevated mice further support critical role immunity. While study only focused on identifying immunity, our data point much broader implication than previously thought. This dedicated Dr. Marc Caron who has left indelible mark field.

Language: Английский

---

Monoamine oxidases: a missing link between mitochondria and inflammation in chronic diseases ?

Redox Biology, Journal Year: 2024, Volume and Issue: 77, P. 103393 - 103393

Published: Oct. 11, 2024

The role of mitochondria spans from the regulation oxidative phosphorylation, cell metabolism and survival/death pathways to a more recently identified function in chronic inflammation. In stress situations, release some pro-inflammatory mediators such as ATP, cardiolipin, reactive oxygen species (ROS) or mitochondrial DNA, that are believed participate diseases aging. These Damage-Associated Molecular Patterns (mito-DAMPs) can modulate specific receptors among which TLR9, NLRP3 cGAS-STING, triggering immune cells activation sterile order counter development diseases, better understanding underlying mechanisms low grade inflammation induced by mito-DAMPs is needed. this context, monoamine oxidases (MAO), enzymes degrade catecholamines serotonin, have emerged potent regulators obesity-related disorders, cardiac cancer, rheumatoid arthritis pulmonary diseases. these embraces their action both non-immune cells, where they regulate monoamines levels generate toxic ROS aldehydes, by-products enzymatic reaction. Here, we discuss recent advances on MAOs inflammatory

Language: Английский

---

Repetitive transcranial magnetic stimulation alleviates motor impairment in Parkinson’s disease: association with peripheral inflammatory regulatory T-cells and SYT6

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: Oct. 25, 2024

Abstract Background Repetitive transcranial magnetic stimulation (rTMS) has been used to treat various neurological disorders. However, the molecular mechanism underlying therapeutic effect of rTMS on Parkinson’s disease (PD) not fully elucidated. Neuroinflammation like regulatory T-cells (Tregs) appears be a key modulator progression in PD. If affects peripheral Tregs PD remains unknown. Methods Here, we conducted prospective clinical study (Chinese ClinicalTrials. gov: ChiCTR 2100051140) involving 54 patients who received 10-day (10 Hz) primary motor cortex (M1) region or sham treatment. Clinical and function assessment as well flow cytology were undertaken consecutively recruited from department neurology at Zhujiang hospital between September 2021 January 2022. Subsequently, implemented cytometry analysis examine population spleen MPTP-induced mice that treatment, along with quantitative proteomic approach reveal novel targets for Parkinson's disease, finally, RNA interference method verifies role these new treatment Results We demonstrated M1 significantly improved dysfunction patients. The beneficial effects persisted up 40 days, associated an increase Tregs. There was positive correlation improvements cases. Similarly, brains ameliorated symptoms. reversed downregulation circulating tyrosine hydroxylase neurons mice. It also increased anti-inflammatory mediators, deactivated microglia, decreased inflammatory cytokines. These blocked by administration Treg inhibitor anti-CD25 antibody Quantitative identified TLR4, TH, Slc6a3 especially Syt6 hub node proteins related therapy. Lastly, validated rTMS-related protein syt6 MPTP using virus method. Conclusions Our experimental studies suggest improves modulating suppressing toxic neuroinflammation. Hub (especially Syt6) may potential targets. Trial registration Chinese ClinicalTrials, ChiCTR2100051140. Registered 15 December 2021, https://www.chictr.org.cn/bin/project/edit?pid=133691 Graphical is safe non-invasive disease. In this study, showed proportion CD4+CD25+CD127- blood after Similar verified Proteomic analyses can modulated therapy

Language: Английский

---

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

---