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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Management of HIV in the older adults: Clinical and public health challenge

Public Health Nursing, Journal Year: 2024, Volume and Issue: 41(3), P. 406 - 415

Published: Feb. 7, 2024

Abstract As a result of significant advances in antiretroviral therapy (ART), the number people living with human immunodeficiency virus (PLWH) who are alive well into their senior years has increased significantly recent years. While life expectancy is highly desired outcome for PLWH, it brings challenges that only now starting to be understood and fully appreciated. These include higher rates co‐morbidities, polypharmacy, drug side effects, cognitive deficits, as numerous psychosocial issues such stigma, loneliness, depression. Older PLWH also face related housing, health insurance, long‐term care. This review will discuss many faced by older present clinical public responses suggested interventions may improve outcomes this population.

Language: Английский

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Multimodal Approach to Neurocognitive Function in People Living with HIV in the cART Era: A Comprehensive Review

Life, Journal Year: 2024, Volume and Issue: 14(4), P. 508 - 508

Published: April 15, 2024

Combination antiretroviral treatment (cART) has revolutionized the management of human immunodeficiency virus (HIV) and markedly improved disease burden life expectancy people living with HIV. HIV enters central nervous system (CNS) early in course infection, establishes latency, produces a pro-inflammatory milieu that may affect cognitive functions, even cART era. Whereas severe forms neurocognitive impairment (NCI) such as HIV-associated dementia have declined over last decades, milder become more prevalent, are commonly multifactorial, associated comorbidity burdens, mental health, neurotoxicity, ageing. Since 2007, Frascati criteria been used to characterize classify disorders (HAND) into three stages, namely asymptomatic (ANI), mild disorder (MND), (HAD). These based on comprehensive neuropsychological assessment presupposes availability validated, demographically adjusted, normative population data. Novel neuroimaging modalities biomarkers proposed order complement NCI assessments, elucidate neuropathogenic mechanisms, support diagnosis, monitoring, prognosis. By integrating assessments holistic care approach, clinicians can enhance diagnostic accuracy, prognosis, patient outcomes. This review interrogates value these modes proposes unified approach diagnosis.

Language: Английский

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Pananx notoginseng saponins attenuate CCL2-induced cognitive deficits in rats via anti-inflammation and anti-apoptosis effects that involve suppressing over-activation of NMDA receptors

Biomedicine & Pharmacotherapy, Journal Year: 2020, Volume and Issue: 127, P. 110139 - 110139

Published: April 14, 2020

HIV-associated neurocognitive disorders (HAND) are characterized by synaptic damage and neuronal loss in the brain, ultimately leading to progressive decline of cognitive abilities memory. Chemokine CC motif ligand 2 (CCL2) is elevated cerebrospinal fluid (CSF), has been believed contribute HAND. Previous studies our research team have shown that CCL2 enhances N-Methyl-D-aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents (EPSCs) causes nerve cell damage. However, there few drugs currently available treat caused CCL2. Panax notoginseng saponins (PNS) isolated from benefit human body various ways, including neuroprotective effect. protective effect PNS on CCL2-induced neurotoxicity remains unknown. In this study, we found improved learning memory impairment, inhibited death. These effects may be due inhibiting over-activation NMDA receptors alleviating dysfunction glutamate metabolism. Furthermore, PNS-modulated CCL2-inducd intracellular oxidative stress was attenuate inflammation. Additionally, pretreatment evidently apoptotic pathways reducing Bax/BCL-2 ratio caspase-3, 8, 9 expressions. conclusion, study demonstrates provides substantial neuroprotection against neurotoxicity, a novel therapeutic agent HAND or other neurodegenerative diseases.

Language: Английский

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An update on drug–drug interactions between antiretroviral therapies and drugs of abuse in HIV systems

Expert Opinion on Drug Metabolism & Toxicology, Journal Year: 2020, Volume and Issue: 16(11), P. 1005 - 1018

Published: Aug. 26, 2020

Introduction While considerable progress has been made in the fight against HIV/AIDS, to date there not a cure, and millions of people around world are currently living with HIV/AIDS. People HIV/AIDS have substance abuse disorders at higher rates than non-infected individuals, which puts them an increased risk drug–drug interactions.Areas covered Potential interactions reviewed for variety potential drugs abuse, both licit illicit. These include alcohol, cigarettes or other nicotine delivery systems, methamphetamine, cocaine, opioids, marijuana. decreased adherence, modulation drug transporters, metabolic enzymes. We also review relative incidence use these HIV/AIDS.Expert opinion Despite improvements outcomes, disparities outcomes between PLWHA who vs those do still exist. It is critical necessity improve patients work stop abusing abuse.

Language: Английский

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HIV-1 and opiates modulate miRNA profiles in extracellular vesicles

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 9, 2023

Opiate abuse increases the risk of HIV transmission and exacerbates neuropathology by increasing inflammation modulating immune cell function. Exosomal EVs(xEV) contain miRNAs that may be differentially expressed due to infection or opiate abuse. Here we develop a preliminary exosomal-miRNA biomarker profile HIV-infected PBMCs in context use. infected with were treated dosages morphine for 72 hours, culture supernatants collected, exosomes isolated using differential centrifugation. extracted, expression levels determined via Nanostring multiplexed microRNA arrays, analyzed Webgestalt. The effect on neuronal function was measuring calcium. Preliminary findings show HIV-1 altered miRNA PBMC-derived EVs concurrently exposure. MicroRNA, hsa-miR-1246 up-regulated 12-fold presence morphine, relative uninfected control. MN, an X4-tropic strain exposed displayed trend which suggests potential synergistic effects between exposure promoting increase viral replication. Dose-dependent differences observed as result xEVs derived from modulated SH-SY5Y cells, ART-treated PBMCs, exhibited increased viability while SH-SY5Ys decreased compared untreated Exposing resulted significant decrease calcium signaling, treatment PBMCs. Overall, induced exosomes, potentially identifying mechanisms action novel therapeutic targets involved use disorder, neuropathology, TNF signaling pathway, NF-κB autophagy, apoptosis infection.

Language: Английский

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The effect of substance misuse on HIV persistence in the CNS

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 399 - 437

Published: Jan. 1, 2024

Language: Английский

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Something to talk about; crosstalk disruption at the neurovascular unit during HIV infection of the CNS

NeuroImmune Pharmacology and Therapeutics, Journal Year: 2024, Volume and Issue: 3(2), P. 97 - 111

Published: June 1, 2024

Although treatable with antiretroviral therapy, HIV infection persists in people living (PLWH). It is well known that the virus finds refuge places for which medications do not reach therapeutic levels, mainly CNS. clear as PLWH age, likelihood of developing HIV-associated neurological deficits increases. At biochemical level dysfunction manifestation altered cellular function and ineffective intercellular communication. In this review, we examine how signaling brain disrupted context HIV. Specifically, concept blood-brain barrier can be a convergence point crosstalk, explored. Crosstalk between cells neurovascular unit (NVU) (endothelium, pericytes, astrocytes, microglia neurons) critical maintaining proper function. fact, NVU allows rapid matching neuronal metabolic needs, regulation (BBB) dynamics nutrient transport changes to immunosurveillance. This review invites reader conceptually consider BBB router or facilitate better understanding intricate events underpin during associated neuropathology.

Language: Английский

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

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 16, 2022

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

Language: Английский

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Methamphetamine augments HIV-1 gp120 inhibition of synaptic transmission and plasticity in rat hippocampal slices: Implications for methamphetamine exacerbation of HIV-associated neurocognitive disorders

Neurobiology of Disease, Journal Year: 2022, Volume and Issue: 168, P. 105712 - 105712

Published: March 23, 2022

Methamphetamine (Meth) abuse and human immunodeficiency virus type 1 (HIV-1) infection are two major public health problems worldwide. Being frequently comorbid with HIV-1 infection, Meth exacerbates neurocognitive impairment in HIV-1-infected individuals even the era of combined antiretroviral therapy. While a large body research have studied individual effects envelope glycoprotein 120 (gp120) brain, far less has focused on their synergistic influence. Moreover, it is well-documented that hippocampus primary site spatial learning long-term memory formation. Dysregulation activity-dependent synaptic transmission plasticity believed to impair function. To uncover underlying mechanisms for increased incidence severity HIV-1-associated disorders (HAND) patients abuse, we investigated acute (20 μM) gp120 (200 pM) CA1 region young adult male rat hippocampus, brain known be vulnerable infection. Our results showed localized application each alone onto reduced short-term dynamics input-output responses frequency facilitation, attenuated potentiation (LTP) induced by either high stimulation or theta burst stimulation. A augmentation was observed when were applied combination. Paired-pulse facilitation exhibited an altered ratio, suggesting presynaptic action. Further studies revealed involvement microglia NLRP3 inflammasome activation gp120-mediated attenuation LTP. Taken together, our demonstrated augmented LTP hippocampus. Since accepted experimental analog at level, such may underlie exacerbation HAND clinically.

Language: Английский

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