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

Single cell approaches define neural stem cell niches and identify microglial ligands that can enhance precursor-mediated oligodendrogenesis DOI Creative Commons
Ashleigh Willis, Danielle Jeong, Yunlong Liu

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(1), P. 115194 - 115194

Published: Jan. 1, 2025

Language: Английский

Citations

2
Glial Cells as Key Regulators in Neuroinflammatory Mechanisms Associated with Multiple Sclerosis DOI Open Access

Styliani Theophanous,

Irene Sargiannidou, Kleopas A. Kleopa

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9588 - 9588

Published: Sept. 4, 2024

Even though several highly effective treatments have been developed for multiple sclerosis (MS), the underlying pathological mechanisms and drivers of disease not fully elucidated. In recent years, there has a growing interest in studying neuroinflammation context glial cell involvement as is increasing evidence their central role progression. Although communication proper function underlies brain homeostasis maintenance, effects an MS remain complex controversial. this review, we aim to provide overview contribution cells, oligodendrocytes, astrocytes, microglia pathology during both activation orchestration inflammatory mechanisms, well synergistic repair restoration function. Additionally, discuss how understanding may new therapeutic targets either limit progression or facilitate repair.

Language: Английский

Citations

8
Transforming Growth Factor β1 Protects Against Ischemic Demyelination via Regulating Microglial Lipid Metabolism Pathway DOI
Yi Xie, Xinyue Wang, Shuai Liu

et al.

Stroke, Journal Year: 2025, Volume and Issue: unknown

Published: March 31, 2025

BACKGROUND: Chronic cerebral hypoperfusion-induced white matter lesions are an important cause of vascular cognitive impairment in aging life. TGF-β1 (transforming growth factor β1) is widely recognized as a multifunctional cytokine participating numerous pathophysiological processes the central nervous system. In this study, we aimed to evaluate neuroprotective potentials ischemic lesions. METHODS: A mouse model bilateral common carotid artery stenosis was established imitate The agonist pathway continuously applied via intraperitoneal injection. Morris water maze test and gait analysis system were used assess disorders modeling mice. Luxol fast blue staining, immunofluorescence, electron microscopy conducted determine severity demyelinating lesions, microglial activation, dysfunction autophagy-lysosomal microglia. Furthermore, primary cultured microglia exposed extracted myelin debris vitro explore underlying mechanisms. RESULTS: As evaluated by behavioral tests, significantly alleviated disorder stenosis-modeling lesion remyelination process also found be highly improved activation pathway. results immunostaining showed that could ameliorate lipid metabolism myelin-engulfed Mechanistically, debris, administration notably mitigated inflammatory response accumulation intracellular droplets promoting degradation pathway, quantified flow cytometry, immunostaining, Western blot, etc. Yet, application autophagy inhibitor (3-methyladenine) reversed above anti-inflammatory effects TGF-β1. CONCLUSIONS: relieved deficit, microglia-mediated neuroinflammation reducing abnormal droplet Clinically, staged may become potential target promising treatment for impairment.

Language: Английский

Citations

0
Type I collagen secreted in white matter lesions inhibits remyelination and functional recovery DOI Creative Commons
Reiji Yamazaki, Morio Azuma, Yasuyuki Osanai

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 13, 2025

Abstract White matter injury is caused by cerebral blood flow disturbances associated with stroke and demyelinating diseases such as multiple sclerosis. Remyelination induced spontaneously after white injury, but progressive sclerosis are usually characterised remyelination failure. However, the mechanisms underlying impaired in lesions demyelination remain unclear. In current study, we demonstrated that collagen fibres accumulated demyelinated of patients (age range 23–80 years) 80–87 years), suggesting accumulation correlates failure these lesions. To investigate function lesions, generated two types mice. We focal lysolecithin (LPC) injection ischemic endothelin 1 (ET1) into internal capsule. found type I were secreted ET1-induced regeneration chronic phase disease. also showed monocyte-derived macrophages infiltrated from peripheral produced exacerbated microglial activation, astrogliosis, axonal injury. Finally, oligodendrocyte differentiation inhibited presence LPC-induced demyelination. These results suggest regeneration, therefore, modulation metabolism might be a novel therapeutic target for

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
Senescent-like microglia limit remyelination through the senescence associated secretory phenotype DOI Creative Commons
Phillip S. Gross, Violeta Durán‐Laforet, Low Tone Ho

et al.

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

Published: March 7, 2025

The capacity to regenerate myelin in the central nervous system diminishes with age. This decline is particularly evident multiple sclerosis (MS), a chronic demyelinating disease. Whether cellular senescence, hallmark of aging, contributes remyelination impairment remains unknown. Here, we show that senescent cells accumulate within demyelinated lesions after injury, and treatments senolytics enhances young middle-aged mice but not aged mice. In mice, observe upregulation senescence-associated transcripts, primarily microglia macrophages, demyelination, followed by reduction during remyelination. However, factors persist lesions, correlating inefficient Proteomic analysis secretory phenotype (SASP) reveals elevated levels CCL11/Eotaxin-1 which found inhibit oligodendrocyte maturation. These results suggest therapeutic targeting SASP components, such as CCL11, may improve aging MS. impact on authors treatment following demyelination young, these effects are mediated including CCL11.

Language: Английский

Citations

0
Clemastine enhances myelin formation in the striatum and medial prefrontal cortex and improves sociability in a neonatal rat hypoxic-ischemic model DOI
Yu Feng,

Xiaohui Ma,

Xuemei Zong

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 185, P. 117916 - 117916

Published: March 9, 2025

Language: Английский

Citations

0
Multimodal brain cell atlas across the adult macaque lifespan DOI Creative Commons
Xiao Zhang,

Guangyao Lai,

Xiangyu Guo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

SUMMARY High-throughput single-cell omics of non-human primate tissues present a remarkable opportunity to study brain aging. Here, we introduce transcriptomic and chromatin accessibility landscape 1,985,317 cells from eight regions 13 cynomolgus female monkeys spanning adult lifespan including exceptionally old individuals up 29-years old. This dataset uncovers dynamic molecular changes in critical functions such as synaptic communication axon myelination, exhibiting high degree cell type region specificity. We identify the multicellular networks pons medulla previously unrecognized hotspot for Furthermore, comparative analyses with human neurodegeneration datasets highlight both shared distinct mechanisms contributing aging disease. In addition, uncover transcription factors implicated monkey pinpoint aging-regulated loci linked longevity neurodegeneration. spatiotemporal atlas will advance our understanding its broader implications health

Language: Английский

Citations

0
Acute TREM2 inhibition depletes MAFB-high microglia and hinders remyelination DOI Creative Commons
Jinchao Hou, Roberta Magliozzi, Yun Chen

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(13)

Published: March 25, 2025

We investigated the role of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in myelin regeneration brain. TREM2 is a receptor that activates microglia, which are crucial for clearing debris and promoting remyelination. Previous studies mouse model demyelination induced by copper-chelating agent Cuprizone (CPZ) have shown stimulation with monoclonal antibody reduces demyelination, while deleting Trem2 gene mice impairs Here, we blocked function acutely an during both remyelination phases CPZ analyzed impact treatment myelination expression single cells. found blocking depleted distinct population microglia high transcription factor MAFB The loss these MAFB-high was linked to impaired generation myelinating oligodendrocytes. Importantly, identified + acute acute-chronic brain lesions from individuals multiple sclerosis (MS), but not inactive lesions. conclude essential maintaining associated repair. This finding has significant implications understanding demyelinating diseases like MS suggests stimulating could be promising therapeutic approach

Language: Английский

Citations

0
Trem2-deficiency aggravates and accelerates age-related myelin degeneration DOI Creative Commons
Tyler J. McCray,

Logan M. Bedford,

Stephanie J. Bissel

et al.

Acta Neuropathologica Communications, Journal Year: 2024, Volume and Issue: 12(1)

Published: Sept. 19, 2024

Language: Английский

Citations

3