Monoacylglycerol Lipase Inhibitor MJN110 Reduces Neuronal Hyperexcitability, Restores Dendritic Arborization Complexity, and Regulates Reward-Related Behavior in Presence of HIV-1 Tat DOI Creative Commons

Alexis F. League,

Benjamin L. Gorman,

Douglas J. Hermes

et al.

Frontiers in Neurology, Journal Year: 2021, Volume and Issue: 12

Published: Aug. 16, 2021

While current therapeutic strategies for people living with human immunodeficiency virus type 1 (HIV-1) suppress replication peripherally, viral proteins such as transactivator of transcription (Tat) enter the central nervous system early upon infection and contribute to chronic inflammatory conditions even alongside antiretroviral treatment. As demand grows supplemental combat virus-associated pathology presenting frequently HIV-associated neurocognitive disorders (HAND), present study aimed characterize potential utility inhibiting monoacylglycerol lipase (MAGL) activity increase inhibitory at cannabinoid receptor-type receptors through upregulation 2-arachidonoylglycerol (2-AG) downregulation its degradation into proinflammatory metabolite arachidonic acid (AA). The MAGL inhibitor MJN110 significantly reduced intracellular calcium increased dendritic branching complexity in Tat-treated primary frontal cortex neuron cultures. Chronic administration vivo 2-AG levels prefrontal (PFC) striatum across Tat(+) Tat(-) groups restored PFC N-arachidonoylethanolamine (AEA) subjects. Tat expression rate reward-related behavioral task acquisition a novel discriminative stimulus learning cognitive flexibility assay, altered reversal specifically mice rates indistinguishable from controls. Collectively, our results suggest neuroprotective role inhibition reducing neuronal hyperexcitability, restoring arborization complexity, mitigating alterations driven by associated latent HIV-1 infection.

Language: Английский

Where Is Dopamine and how do Immune Cells See it?: Dopamine-Mediated Immune Cell Function in Health and Disease DOI
Stephanie Matt, Peter J. Gaskill

Journal of Neuroimmune Pharmacology, Journal Year: 2019, Volume and Issue: 15(1), P. 114 - 164

Published: May 11, 2019

Language: Английский

Citations

217
Dopamine, Immunity, and Disease DOI Creative Commons

Breana Channer,

Stephanie Matt,

Emily Nickoloff-Bybel

et al.

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

Citations

159
Immunomodulatory Effects of Dopamine in Inflammatory Diseases DOI Creative Commons
Yifei Feng, Yan Lü

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: April 9, 2021

Dopamine (DA) receptor, a significant G protein-coupled is classified into two families: D1-like (D1 and D5) D2-like (D2, D3, D4) receptor families, with further formation of homodimers, heteromers, mosaic. Increasing evidence suggests that the immune system can be affected by nervous neurotransmitters, such as dopamine. Recently, role DA in inflammation has been widely studied, mainly focusing on NLRP3 inflammasome, NF-κB pathway, cells. This article provides brief review structures, functions, signaling pathways receptors their relationships inflammation. With detailed descriptions roles Parkinson disease, inflammatory bowel rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, this theoretical basis for drug development targeting diseases.

Language: Английский

Citations

75
The Impact of Neurotransmitters on the Neurobiology of Neurodegenerative Diseases DOI Open Access
Sarah E. Davis,

Abagail B. Cirincione,

Ana Catya Jiménez-Torres

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15340 - 15340

Published: Oct. 19, 2023

Neurodegenerative diseases affect millions of people worldwide. result from progressive damage to nerve cells in the brain or peripheral nervous system connections that are essential for cognition, coordination, strength, sensation, and mobility. Dysfunction these functions is associated with Alzheimer's disease, Parkinson's Huntington's Amyotrophic lateral sclerosis, motor neuron disease. In addition these, 50% living HIV develop a spectrum cognitive, motor, and/or mood problems collectively referred as HIV-Associated Neurocognitive Disorders (HAND) despite widespread use combination antiretroviral therapies. Neuroinflammation neurotransmitter systems have pathological correlation play critical role developing neurodegenerative diseases. Each has unique pattern dysregulation system, which been attributed different forms cell-specific neuronal loss. this review, we will focus on discussion regulation dopaminergic cholinergic systems, more commonly disturbed disorders. Additionally, provide evidence hypothesis disturbances neurotransmission contribute loss observed Further, highlight dopamine mediator injury context NeuroHIV. This review need further investigate their etiology

Language: Английский

Citations

27
The impact of substance abuse on HIV-mediated neuropathogenesis in the current ART era DOI

Vanessa Chilunda,

Tina M. Calderon, Pablo Martínez-Aguado

et al.

Brain Research, Journal Year: 2019, Volume and Issue: 1724, P. 146426 - 146426

Published: Aug. 29, 2019

Language: Английский

Citations

55
An integrated cytokine and kynurenine network as the basis of neuroimmune communication DOI Creative Commons
Trevor W. Stone, Felix I. L. Clanchy, Yishu Huang

et al.

Frontiers in Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: Nov. 24, 2022

Two of the molecular families closely associated with mediating communication between brain and immune system are cytokines kynurenine metabolites tryptophan. Both groups regulate neuron glial activity in central nervous (CNS) leukocyte function system, although neither group alone completely explains neuroimmune function, disease occurrence or severity. This essay suggests that two perform complementary functions generating an integrated network. The pathway determines overall neuronal excitability plasticity by modulating glutamate receptors GPR35 across CNS, regulates general features cell status, surveillance tolerance which often involves Aryl Hydrocarbon Receptor (AHR). Equally, chemokines define specific populations neurons, glia leukocytes, more responses within restricted CNS regions populations. In addition, as there is a much larger variety these compounds, their homing properties enable superimposition dynamic variations upon local, spatially limited, would principle allow targeting potential treatments to CNS. proposed synergistic interface ‘tonic’ affecting baseline superimposed ‘phasic’ cytokine constitute network explaining some communication. concept broaden scope for development new disorders involving both systems, safer effective agents targeted regions.

Language: Английский

Citations

27
Dopamine and norepinephrine are embracing their immune side and so should we DOI
Peter J. Gaskill, Habibeh Khoshbouei

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

Published: Sept. 1, 2022

Language: Английский

Citations

25
Functional characterization of the biogenic amine transporters on human macrophages DOI Creative Commons
Phillip Mackie, Adithya Gopinath,

Dominic Montas

et al.

JCI Insight, Journal Year: 2022, Volume and Issue: 7(4)

Published: Jan. 11, 2022

Monocyte-derived macrophages (MDMs) are key players in tissue homeostasis and diseases regulated by a variety of signaling molecules. Recent literature has highlighted the ability for biogenic amines to regulate macrophage functions, but mechanisms governing amine around immune cells remain nebulous. In CNS, transporters regarded as master regulators neurotransmitter signaling. While we others have shown that express these transporters, relatively little is known their function cells. To address knowledge gaps, investigated norepinephrine transporter (NET) dopamine (DAT) on human MDMs. We found both NET DAT present can uptake substrate from extracellular space at baseline. Not only was expressed cultured MDMs, it also detected subset intestinal situ. Surprisingly, discovered NET-independent, DAT-mediated immunomodulatory mechanism response LPS. LPS induced reverse transport through DAT, engaging an autocrine/paracrine loop response. Removing this enhanced proinflammatory Our data introduce potential role regulation innate immunity.

Language: Английский

Citations

24
Dopamine activates NF-κB and primes the NLRP3 inflammasome in primary human macrophages DOI Creative Commons
Rachel Nolan,

Katelyn Reeb,

Yongzhang Rong

et al.

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

Citations

39
HIV Neuropathogenesis in the Presence of a Disrupted Dopamine System DOI

Emily Nickoloff-Bybel,

Tina M. Calderon, Peter J. Gaskill

et al.

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

Published: June 6, 2020

Language: Английский

Citations

35