Peripheral blood cytokines as markers of longitudinal recovery in white matter microstructure following inpatient treatment for opioid use disorders DOI Creative Commons

Eduardo R Butelman,

Yuefeng Huang,

Sarah King

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 9, 2024

Abstract Background Heroin and other opioid use disorders (HUD OUD) cause massive public health morbidity mortality. Although standard-of-care medication assisted treatment (MAT) exists, little is known about potential predictors of change during recovery. Recovery can include normalization the brain’s white matter (WM) microstructure, which sensitive to cytokine immune signaling. Here we aimed determine whether blood-based cytokine/immune markers predict WM microstructure recovery following medication-assisted treatment. Methods Inpatient Individuals with HUD (iHUD; n=21) healthy controls (HC; n=24) underwent magnetic resonance scans diffusion tensor imaging (DTI) provided ratings drug cue-induced craving, arousal valence twice, earlier in ≈14 weeks inpatient MAT (with methadone or buprenorphine) thereafter. At this second session (MRI2), they also a peripheral blood sample for multiplex relative quantification serum proteins proximity extension assay, Olink). We explored correlation multi-target biomarker score (based on principal component analysis 19 that differed significantly between iHUD HC) whole-brain DTI (ΔDTI; MRI2 - MRI1) metrics (fractional anisotropy, mean diffusivity, axial diffusivity) across 14 MAT. Results The score, obtained at stage, was correlated ΔDTI frontal, fronto-parietal, cortico-limbic tracts (e.g., including genu corpus callosum, anterior corona radiata, others). In follow-up analysis, specific cytokines represented such as interleukin oncostatin M (OSM), colony stimulating factor (CSF21), chemokine CCL7 were similar iHUD, but not HC. Levels (i.e., CCL19 CCL2) negatively craving arousal. Thus, lower levels aforementioned an increase two stages (MRI2 MRI1). Conclusions Studied individual targets, are highly accessible biomarkers undergoing

Language: Английский

Glucose Metabolic Reprogramming in Microglia: Implications for Neurodegenerative Diseases and Targeted Therapy DOI
Mengqi Fang, Yuan Zhou,

Keren He

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 22, 2025

Language: Английский

Citations

0
Peripheral blood cytokines as markers of longitudinal change in white matter microstructure following inpatient treatment for opioid use disorders DOI Creative Commons

Eduardo R Butelman,

Yuefeng Huang,

Sarah King

et al.

Biological Psychiatry Global Open Science, Journal Year: 2025, Volume and Issue: unknown, P. 100480 - 100480

Published: March 1, 2025

Opioid use disorder (OUD) causes major public health morbidity and mortality. Although standard-of-care treatment with medications for OUD (MOUDs) is available, there are few biological markers of the clinical process recovery. Neurobiological aspects recovery can include normalization brain white matter (WM) microstructure, which sensitive to cytokine signaling. Here, we determined whether blood-based cytokines be change in WM microstructure following MOUD. Inpatient individuals heroin (iHUDs) (n = 21) methadone or buprenorphine MOUD underwent magnetic resonance imaging (MRI) scans diffusion tensor (DTI) provided ratings drug cue-induced craving, arousal, valence earlier (MRI1) ≈14 weeks thereafter (MRI2). Healthy control participants (HCs) 24) also 2 MRI during a similar time interval. At MRI2, peripheral blood sample multiplex quantification serum cytokines. We analyzed correlation multitarget biomarker score (from principal component analysis 19 that differed significantly between iHUDs HCs) treatment-related DTI metrics (ΔDTI; MRI2 - MRI1). The was negatively correlated ΔDTI frontal, frontoparietal, corticolimbic tracts but not HCs. Also, levels specific score, including interleukin-related oncostatin M (OSM), similarly Serum other were changes craving arousal iHUDs. Specific cytokines, studied alone as group, may serve accessible biomarkers potential undergoing

Language: Английский

Citations

0
Oligodendroglial precursor cells modulate immune response and early demyelination in a murine model of multiple sclerosis DOI
Qi Wang, Taida Huang, Zihan Zheng

et al.

Science Translational Medicine, Journal Year: 2025, Volume and Issue: 17(792)

Published: April 2, 2025

Reproducing the pathophysiology of human multiple sclerosis (MS) in animal models is critical to identifying mechanisms triggering demyelination and developing early intervention strategies. Here, we aimed model overactivated Wnt (wingless-related integration site) signaling previously shown postmortem brain tissues patients with MS by inducing experimental autoimmune encephalomyelitis (EAE) Pdgfra CreER ;Apc fl/fl Olig2 Cre mice. These mice have oligodendrocyte precursor cells (OPCs) because a conditional knockout pathway repressor adenomatous polyposis coli (APC). EAE exhibited increased expression markers for activation such as Axis inhibition protein 2 (AXIN2) inhibitory factor 1 (WIF1) OPCs showed exacerbated progression both spinal cord brain. Genetic or antibody-mediated ablation CC-chemokine ligand 4 (CCL4) prevented infiltration CD4 + T arrested disease these A characterization CNS (central nervous system) immune cell clusters identified an augmented subpopulation NK1.1 CD11b Gr-1 cytotoxic macrophages Microinjection this into brains wild-type C57/B6J was sufficient induce demyelination. Ablation effects overactivation on infiltration. Antagonizing chemokine receptor 5 (CCR5) using European Medicines Agency–approved drug, maraviroc, reduced infiltration, alleviated demyelination, attenuated progression. We found OPC-orchestrated cellular network that instigates provides insight pathophysiology, suggests avenues interventions.

Language: Английский

Citations

0
Myelopoiesis is temporally dynamic and is regulated by lifestyle to modify multiple sclerosis DOI Creative Commons
Abi G. Yates, Annie Khamhoung,

Lena Gaebel

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 17, 2025

Monocytes and neutrophils from the myeloid lineage contribute to multiple sclerosis (MS), but dynamics of myelopoiesis during MS are unclear. Here we uncover a disease stage-specific relationship between lifestyle, neuroinflammation. In mice with relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE), in femur, vertebrae spleen is elevated prior onset remission, preceding peaks clinical disability progressive EAE (P-EAE), vertebral rises steadily throughout disease, while femur splenic early before waning later height. parallel, sleep disruption or hyperlipidemia cardiometabolic syndrome augment M-CSF generation multi-organ worsen P-EAE symptoms, neuroinflammation, spinal cord demyelination, blockade abrogating these symptoms. Lastly, results previous trial show that Mediterranean diet restrains myelopoietic activity progenitor skewing improves symptomology MS. Together, our data suggest dynamic dependent on stage location, lifestyle factors modulate by influencing M-CSF-mediated myelopoiesis.

Language: Английский

Citations

0
Drp1 mitochondrial fission in astrocyte modulates behavior and neuroinflammation during morphine addiction DOI Creative Commons

Xiaotong Gu,

Wenjing Chen, Zixin Li

et al.

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

Published: April 17, 2025

Mitochondrial dynamics in neurons accompanied by neuroinflammation has been proved as pivotal events during repeated morphine exposure, however, the relationship between mitochondrial and still remains unknown. This study was designed to investigate potential role of astrocyte Drp1 addiction. Nucleus accumbens (NAc) tissues were collected for immunofluorescence, transmission electron microscopy (TEM) quantitative real-time polymerase chain reaction (qRT-PCR) detect expression pro-inflammatory cytokines fission proteins. Morphine-induced conditioned place preference (CPP) open field test (OFT) used determine effects Mdivi-1, a selective inhibitor protein rewarding properties morphine. Astrocyte-specific knockdown experiments an adeno-associated virus (AAV) vector containing shRNADrp1-EGFP infusion performed NAc mice with treatment. In this study, we found that exposure induced fragmentation neurons, astrocytes, microglia NAc, correlating increased inflammatory markers addictive behaviors. The application Mdivi-1 effectively mitigated astrocyte-mediated within thereby alleviating morphine-induced Crucially, astrocyte-specific significantly curtailed drug-seeking behavior substantially reduced neuroinflammation. Collectively, our findings suggest alterations dynamics, particularly play important regulating associated research offers novel insights into therapeutic strategies addressing substance use disorder (SUD) astrocyte.

Language: Английский

Citations

0
E3 ubiquitin ligase RNF128 negatively regulates the IL-3/STAT5 signaling pathway by facilitating K27-linked polyubiquitination of IL-3Rα DOI Creative Commons

Jingge Yu,

Jianguo Li, Ao Shen

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 3, 2024

Abstract IL-3/STAT5 signaling pathway is crucial for the development and activation of immune cells, contributing to cellular response infections inflammatory stimuli. Dysregulation have been associated with autoimmune diseases characterized by cell infiltration organ damage. IL-3 receptor α (IL-3Rα) specifically binds initiates intracellular signaling, resulting in phosphorylation STAT5. However, regulatory mechanisms IL-3Rα remain unclear. Here, we identified E3 ubiquitin ligase RNF128 as a negative regulator targeting lysosomal degradation. was shown selectively bind IL-3Rα, without interacting common beta chain IL-3Rβ, which shares subunit GM-CSF. The deficiency Rnf128 had no effect on GM-CSF-induced Stat5, but it resulted heightened Il-3-triggered Stat5 increased transcription Id1 , Pim1 Cd69 genes. Furthermore, found that promoted K27-linked polyubiquitination activity-dependent manner, ultimately facilitating its degradation through pathway. inhibited chemotaxis macrophages LPS stimulation, thereby attenuating excessive responses. Collectively, these results reveal negatively regulates IL-3Rα. This study uncovers novel pathway, providing potential molecular targets treatment diseases.

Language: Английский

Citations

3
IL-3: key orchestrator of inflammation DOI Creative Commons

Malgorzata J. Podolska,

Robert Grützmann, Christian Pilarsky

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 13, 2024

Interleukin (IL)-3 has long been known for its hematopoietic properties. However, recent evidence expanded our understanding of IL-3 function by identifying as a critical orchestrator inflammation in wide array diseases. Depending on the type disease, course inflammation, cell or tissue involved, promotes either pathologic resolution. Here, we describe cell-specific functions and summarize role We discuss current treatments targeting receptor, highlight potential limitations clinics.

Language: Английский

Citations

3
X-chromosome linked genes associated with myeloid cell CNS trafficking contributes to female–male differences in the disease outcome for neuroinflammatory diseases DOI

Sopiko Darchiashvili,

Ratuja Kulkarni,

Ritesh Tandon

et al.

NeuroImmune Pharmacology and Therapeutics, Journal Year: 2024, Volume and Issue: 3(2), P. 71 - 95

Published: June 1, 2024

Abstract Certain diseases such as Multiple Sclerosis (MS), a chronic demyelinating disease, affect more women than men, despite males appearing to be predisposed infections and malignancies. X-linked genes contribute increased MS susceptibility. Currently, an immense body of research exists that explores the complexity surrounding underlying risk factors for development including X-chromosome-linked inflammatory processes. Female–male disparities in disease susceptibility have been found at both gene chromosomal level. Genes CXORF21 DDX3X can escape X-chromosome inactivation (XCI) various pathogenesis. Additionally, blocking immune cell entry central nervous system (CNS) major impact on MS. Prior has shown cells T dendritic (DCs) infiltrate CNS. Due persistent tissue stress, these may induce local inflammation autoimmunity, subsequent neurodegeneration, onset progression Chemokines are signaling proteins which regulate leukocyte trafficking site injury, contributing recruitment, CNS inflammation, severity. Some chemokine receptors (CXCR3) XCI. This review provides account contribution x-linked relation chemotaxis myeloid into neuroinflammation. The XCI expression is evaluated. Collectively, analyses from this seek advance our understanding advocate patient-specific therapies.

Language: Английский

Citations

3
Nanotherapeutic Approaches of Interleukin‐3 to Clear the α‐Synuclein Pathology in Mouse Models of Parkinson's Disease DOI Creative Commons
Wenlong Zhang, Jian Ren,

Liuyan Ding

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 3, 2024

Abstract Astrocyte‐microglia crosstalk is vital for neuronal survival and clearing aggregate accumulation in neurodegenerative diseases. While interleukin‐3 (IL‐3) has been reported to exert both protective detrimental effects diseases, however, its role α‐synuclein pathology remains unclear. In this study, it found that astrocytic IL‐3 microglial IL‐3R are positively responsive the brains of transgenic A53T Parkinson's disease (PD) mice an adeno‐associated virus (AAV)‐human (AAV‐ h α‐Syn)‐injected PD mouse model. Exogenous infusion reduces behavioral abnormities nigrostriatal pathology. Mechanistically, induces phagocytosis pathological while simultaneously stimulating dopaminergic (DA) neurons clear via induction autophagy through IFN‐β/Irgm1 pathway. Due limited efficiency crossing blood–brain barrier, a precise delivery strategy developed by cross‐linking RVG29 with PEG‐Linker (RVG‐modified nanogels—RVG‐IL3 NGs). Intravenous administration RVG‐IL3 NGs shows efficient uptake microglia DA within brain. ameliorate motor deficits improving function AAV‐ α‐Syn model PD. Collectively, may represent feasible therapeutic

Language: Английский

Citations

1
Monocyte-derived cells but not Microglia cause Oxidative Tissue Damage in Neuroinflammation DOI
Juan Villar-Vesga, Donatella De Feo,

Pauline Clément

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 22, 2024

Abstract Multiple sclerosis (MS) is characterized by neuroinflammation, oxidative stress, iron toxicity and mitochondrial dysfunction. Reactive oxygen species (ROS) produced mononuclear phagocytes (MPs) are widely held to drive tissue damage, yet the specific roles of central nervous system (CNS)- resident versus CNS-invading MPs remain unclear. Here, combining single-cell profiling with conditional gene targeting, we systematically dissected interfered ROS production across CNS in a preclinical model for neuroinflammation. We show that monocyte derived cells (MdCs) exhibit higher stress signature produce more compared CNS-resident microglia. While NADPH oxidase 2 (NOX2), phagocytic source ROS, proved redundant, our findings underscore critical role (mtROS) driving damage. Quenching mtROS through mitocatalase overexpression MdCs, but not microglia, significantly alleviated neuroinflammation mice. Thus, study resolves longstanding controversy, identifying MdCs as primary driver ROS-mediated neuropathology.

Language: Английский

Citations

1