Glial Cells as Key Regulators in Neuroinflammatory Mechanisms Associated with Multiple Sclerosis

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

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Deterioration of neuroimmune homeostasis in Alzheimer’s Disease patients who survive a COVID-19 infection

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Aug. 17, 2024

Growing evidence has implicated systemic infection as a significant risk factor for the development and advancement of Alzheimer's disease (AD). With emergence SARS-CoV-2 (COVID-19) resultant pandemic, many individuals from same aging population vulnerable to AD suffered severe with potentially unidentified long-term consequences survivors. To study impact COVID-19 survival on brain's intrinsic immune system in also suffering AD, we profiled post-mortem brain tissue patients UF Neuromedicine Human Brain Tissue Bank diagnosis who survived (COVID-AD) contrasted our findings did not experience infection, including group donors passed away before arrival United States. We assessed disease-relevant protein pathology microglial astrocytic markers by quantitative immunohistochemistry supplemented these data whole gene expression analysis performed NanoString nCounter

Language: Английский

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Characterization of Chitinase 3-like protein 1 spatiotemporal distribution in human post-traumatic brain contusions and other neuropathological scenarios

Journal of Neuropathology & Experimental Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Abstract Chitinase 3-like protein 1 (CHI3L1) is emerging as a promising biomarker for assessing intracranial lesion burden and predicting prognosis in traumatic brain injury (TBI) patients. Following experimental TBI, Chi3l1 transcripts were detected reactive astrocytes located within the pericontusional cortex. However, cellular sources of CHI3L1 response to hemorrhagic contusions human remain unidentified. Hence, we examined comprehensive collection histologically defined acute subacute cerebral with various surgical intervals using immunohistochemistry, validated through double immunofluorescence markers such GFAP, NeuN, MBP, Iba-1, along Fluoro-Jade C histofluorescence staining. was found at meningeal interfaces, showing significant thickening subpial glial plate. Paradoxically, CHI3L1-positive identified neuroanatomical locations distant from foci, where numerous eosinophilic ischemic neurons also exhibited immunoreactivity. immunostaining extended into white matter tracts highlighted phagocytic or activated microglia forms after delayed decompressions. Given these findings, advise against astrogliosis marker due its expression multiple cell types, including astrocytes, neurons, oligodendrocytes, ependymocytes, leptomeningeal cells, microglia, blood vessels. This non-selective underscores potential elevation patterns biofluids reflect overall extent.

Language: Английский

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Multi-omic Characterization of HIV Effects at Single Cell Level across Human Brain Regions

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

Published: Feb. 8, 2025

Abstract HIV infection exerts profound and long-lasting neurodegenerative effects on the central nervous system (CNS) that can persist despite antiretroviral therapy (ART). Here, we used single-nucleus multiome sequencing to map transcriptomic epigenetic landscapes of postmortem human brains from 13 healthy individuals 20 with who have a history treatment ART. Our study spanned three distinct regions—the prefrontal cortex, insular ventral striatum—enabling comprehensive exploration region-specific cross-regional perturbations. We found widespread persistent HIV-associated transcriptional alterations across multiple cell types. Detailed analyses microglia revealed state changes marked by immune activation metabolic dysregulation, while integrative multiomic profiling astrocytes identified subpopulations, including reactive subpopulation unique HIV-infected brains. These findings suggest cells people exhibit molecular shifts may underlie ongoing neuroinflammation CNS dysfunction. Furthermore, cell–cell communication uncovered dysregulated pro-inflammatory interactions among glial populations, underscoring multifaceted enduring impact brain milieu. Collectively, our atlas reveals states signatures signaling providing framework for developing targeted therapies neurological

Language: Английский

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Single-cell analysis of CD14+CD16+ monocytes identifies a subpopulation with an enhanced migratory and inflammatory phenotype

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 20, 2025

Monocytes in the central nervous system (CNS) play a pivotal role surveillance and homeostasis, can exacerbate pathogenic processes during injury, infection, or inflammation. CD14+CD16+ monocytes exhibit diverse functions contribute to neuroinflammatory diseases, including HIV-associated neurocognitive impairment (HIV-NCI). Analysis of human matured vitro by single-cell RNA sequencing identified heterogenous population nine clusters. Ingenuity pathway analysis differentially expressed genes each cluster increased migratory inflammatory pathways for group clusters, which we termed Group 1 monocytes. monocytes, distinguished ALCAM, CD52, CD63, SDC2, exhibited gene expression signatures implicated CNS produced higher levels CXCL12, IL-1Ra, IL-6, IL-10, TNFα, ROS, preferentially transmigrated across blood-brain barrier model. Thus, cells within monocyte subset are likely be major contributors diseases.

Language: Английский

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Chitinase-3 Like-Protein-1 Signature in Neurological Disorders: Emphasis on Stroke

Journal of Molecular Neuroscience, Journal Year: 2025, Volume and Issue: 75(1)

Published: Feb. 20, 2025

Language: Английский

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Implications of Chitinase 3-like 1 Protein in the Pathogenesis of Multiple Sclerosis in Autopsied Brains and a Murine Model

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4160 - 4160

Published: April 27, 2025

Chitinase-3-like protein 1 (CHI3L1) has been implicated in multiple sclerosis (MS) pathology, yet its precise role remains unclear. To elucidate involvement, we performed proteomic analysis of cerebrospinal fluid (CSF) from relapsing-remitting MS (RRMS) patients using two-dimensional difference gel electrophoresis (2D-DIGE). CHI3L1 emerged as the most upregulated recurrent RRMS. ELISA confirmed significantly elevated levels RRMS and secondary progressive (SPMS) patients, with decreasing steroid responders but increasing non-responders. Immunohistochemistry brain autopsies revealed expression predominantly mature oligodendrocytes. In an experimental autoimmune encephalomyelitis (EAE) model, was highly expressed spinal cord, particularly oligodendrocytes microglia/macrophages. Functional studies demonstrated that recombinant (rCHI3L1) protected LPC-induced cell death by attenuating ER stress (GRP78, ORP150). Moreover, rCHI3L1 counteracted IFN-β- PSL-mediated inhibition oligodendrocyte differentiation. microglia, suppressed LPS-induced proinflammatory markers (IL-1β, iNOS). vivo, administration mitigated EAE severity reducing gliosis, demyelination, axonal degeneration. These findings highlight a critical modulator neuroinflammation survival, positioning it promising therapeutic target for MS.

Language: Английский

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Plasma CHI3L1 associates with brain volume loss and glial activation in multiple sclerosis

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2025, Volume and Issue: unknown, P. jnnp - 336063

Published: May 16, 2025

Multiple sclerosis (MS) progression independent of relapses is driven by brain innate immune cell activation. The aim this study was to evaluate the association between chitinase-3-like protein 1 (CHI3L1), expressed in astrocytes and microglia, measured from blood smouldering inflammation using 18 kDa translocator (TSPO) positron emission tomography (PET) patients with MS. cohort included 55 MS (25 progressive (PMS) 30 relapsing remitting (RRMS)) 17 healthy controls (HC). CHI3L1 commercial ELISA plasma samples. A subcohort (44 9 HC) underwent TSPO-PET assess [11C]PK11195 distribution volume ratio (DVR) MRI concurrent sampling. These imaging outcomes were used respective correlation linear regression analyses. concentration higher PMS (23.5 ng/mL) compared HC (16.8 ng/mL, p=0.0055) RRMS (19.3 p=0.049). associated DVR all (standardised estimate 0.89, 95% CI 0.23 1.55, p=0.010) (Spearman ρ=0.58, 0.058 0.86, p=0.032). Additionally, smaller both (-0.75, -1.38 -0.11, p=0.023) (ρ=-0.56, -0.83 -0.095, p=0.021). Furthermore, Expanded Disability Status Scale (0.70, 0.12 1.28, p=0.019) age (0.93, 0.37 1.48, p=0.002) among Association glial activation loss identifies as a promising biomarker for progression-related pathology.

Language: Английский

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CHI3L1 in Multiple Sclerosis—From Bench to Clinic

Cells, Journal Year: 2024, Volume and Issue: 13(24), P. 2086 - 2086

Published: Dec. 17, 2024

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) with complex and not fully understood etiopathological background involving inflammatory neurodegenerative processes. CHI3L1 has been implicated in pathological conditions such as inflammation, injury, neurodegeneration, likely to play role physiological development CNS. primarily produced by CNS macrophages, microglia, activated astrocytes. The expression pattern MS lesions might support important astrocytes modulating processes this disease. potential applications biomarker are multifactorial. measurement body fluids find its early diagnosis MS. In further stages, monitoring levels provide information on severity progression, enabling better adjustment therapeutic strategies. Importantly, potentially serve marker ongoing glial activation, reflecting dynamic response cells Although preliminary findings have promising, research needed validate utility measurements prediction progression Additionally, comparisons other biomarkers be useful clinical practice.

Language: Английский

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Protocol to establish a demyelinated animal model to study hippocampal neurogenesis and cognitive function in adult rodents

STAR Protocols, Journal Year: 2024, Volume and Issue: 5(3), P. 103242 - 103242

Published: Aug. 1, 2024

Cognitive dysfunction is a prevalent feature in multiple sclerosis, chronic inflammatory demyelinating disease, which may be correlated with the impairment of adult hippocampal neurogenesis. Here, we present detailed protocol for induction cuprizone demyelinated mice to assess cognitive function and explore precise mechanisms underlying deficits hippocampus. We describe steps behavioral tests, 5-Ethynyl-2'-deoxyuridine (EdU) bromodeoxyuridine (BrdU) administration, retrovirus packaging stereotactic injection, tissue preparation, immunofluorescence staining. For complete details on use execution this protocol, please refer Song et al.

Language: Английский

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