A5033616546- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Response and Inflammation
- Immune cells in cancer
- Neurogenesis and neuroplasticity mechanisms
- Immunotherapy and Immune Responses
- Stress Responses and Cortisol
- Immune Cell Function and Interaction
- Alzheimer's disease research and treatments
- Diet and metabolism studies
- Cancer-related molecular mechanisms research
- Drug Transport and Resistance Mechanisms
- Neurological Disease Mechanisms and Treatments
- Receptor Mechanisms and Signaling
- Circular RNAs in diseases
- Cell Adhesion Molecules Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Systemic Lupus Erythematosus Research
- Extracellular vesicles in disease
- interferon and immune responses
- Adenosine and Purinergic Signaling
- Mast cells and histamine
- Inflammasome and immune disorders
- Cytokine Signaling Pathways and Interactions
- Gastroesophageal reflux and treatments
- Cancer Immunotherapy and Biomarkers
Université Laval
2012-2024
Centre hospitalier universitaire de Québec
2014-2024
Wilfrid Laurier University
1996-2024
Imagerie et Cerveau
2022
University of Victoria
2022
Centre hospitalier de l'Université Laval
2014
The University of Texas MD Anderson Cancer Center
2013
Institut Pasteur
2013
Endocrinology Research Center
2004
Salk Institute for Biological Studies
2002-2003
Postnatal neurogenesis can be modulated after brain injury, but the role of attendant expression inflammatory mediators in such responses remains to determined. Here we report that transgenically directed production interleukin-6 (IL-6) by astroglia decreased overall 63% hippocampal dentate gyrus young adult transgenic mice. The proliferation, survival, and differentiation neural progenitor cells labeled with thymidine analog bromodeoxyuridine were all reduced granule cell layer these mice,...
The past decade has witnessed a revolution in our understanding of microglia. These immune cells were shown to actively remodel neuronal circuits, leading propose new pathogenic mechanisms. To study microglial implication the loss synapses, best pathological correlate cognitive decline across chronic stress, aging, and diseases, we recently conducted ultrastructural analyses. Our work uncovered existence phenotype that is rarely present under steady state conditions, hippocampus, cerebral...
Interleukin-6 (IL-6) is a pleiotropic cytokine believed to play key roles in the neuroimmune interactions. This molecule may act on nervous system by interacting with its specific receptor subunit (IL-6R) and signal transducer gp130. The purposes of present study were describe central distribution IL-6, IL-6R, gp130 mRNAs under basal conditions verify influence immune activator lipopolysaccharide (LPS) proinflammatory interleukin-1beta (IL-1beta) expression IL-6 related genes throughout rat...
Cytogenesis in the adult brain can result from recruitment of circulating precursors, but proposal that some such cells transdifferentiate into neural elements is controversial. We have reinvestigated this issue by following phenotypic fate bone marrow expressing green fluorescent protein transplanted systemic circulation irradiated mice. Thousands donor-derived were detected throughout brains recipients killed 1-12 months after transplantation, none displayed neuronal, macroglial, or...
A broad spectrum of diseases is characterized by myelin abnormalities and/or oligodendrocyte pathology. In most, if not all, these diseases, early activation microglia occurs. Our knowledge regarding the factors triggering is, however, incomplete. this study, we used cuprizone model to investigate temporal and causal relationship apoptosis activation. Genome-wide gene expression studies revealed induction distinct chemokines, among them Cxcl10, Ccl2, Ccl3 in cuprizone-mediated apoptosis....
Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by deposition of extracellular fibrillar amyloid β (fΑβ) and intracellular accumulation neurofibrillary tangles. As AD progresses, Aβ drives a robust prolonged inflammatory response via its recognition microglia, brain's immune cells. Microglial reactivity to fAβ plaques may impair their normal surveillance duties, facilitating synaptic loss neuronal death, as well cognitive decline in AD.In current study,...
A diverse heterogeneity of microglial cells was previously described in Alzheimer's disease (AD) pathology, including dark microglia, a state characterized by ultrastructural markers cellular stress. To provide novel insights into the roles microglia during aging context AD we performed quantitative density and analysis these using high-throughput scanning electron microscopy ventral hippocampus CA1 stratum lacunosum-moleculare 20-month-old APP-PS1 vs C57BL/6J male mice. The significantly...
Interleukin-6 (IL-6) is a proinflammatory cytokine that plays multiple roles in the central nervous system during infections and injuries. Although this molecule capable of stimulating release ACTH glucocorticoids, it has been demonstrated single injection IL-6 fails to activate paraventricular nucleus (PVN) neurons control hypothalamic-pituitary-adrenal axis. The observation receptor (IL-6R) up-regulated brain endotoxemia led us hypothesize prior induction IL-6R synthesis could amplify...
Abstract G protein‐coupled receptor 84 (GPR84) is a recently discovered member of the seven transmembrane superfamily whose function and regulation are unknown. Here, we report that in mice suffering from endotoxemia, microglia express GPR84 strong sustained manner. This property shared by subpopulations peripheral macrophages and, to much lesser extent, monocytes. The induction expression endotoxin mediated, at least part, proinflammatory cytokines, notably tumor necrosis factor (TNF)...
Abstract Macrophages can promote the growth of some tumors, such as those breast and lung, but it is unknown whether this true for all including nervous system. On contrary, we have previously shown that macrophages slow progression malignant gliomas through a tumor necrosis factor–dependent mechanism. Here, provide evidence suggesting antitumor effect could be mediated by T lymphocytes, their number was drastically reduced in factor–deficient mice inversely correlated with glioma volume....
Abstract Background Granulocytes generally exert protective roles in the central nervous system (CNS), but recent studies suggest that they can be detrimental experimental autoimmune encephalomyelitis (EAE), most common model of multiple sclerosis. While cytokines and adhesion molecules involved granulocyte to brain vasculature have started elucidated, required chemokines remain undetermined. Methods CXCR2 ligand expression was examined CNS mice suffering from EAE or exposed bacterial toxins...
Microbial agents can aggravate inflammatory diseases, such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). An example is pertussis toxin (PTX), a bacterial virulence factor commonly used an adjuvant to promote EAE, but whose mechanism of action unclear. We have reported that PTX triggers IL-6-mediated signaling cascade increases the number leukocytes patrol vasculature by crawling on luminal surface. In present study, we examined this...
Dysregulation of miRNAs has been observed in many neurodegenerative diseases, including multiple sclerosis. Morquette et al. show that overexpression miR-223-3p prevents accumulation axonal damage a rodent model sclerosis, part through regulation glutamate receptor signalling. Manipulation miRNA levels may have therapeutic potential.
Abstract Microglia, monocytes, and peripheral macrophages share a common origin many characteristics, but what distinguishes them from each other at the level of gene expression remains largely unknown. In this study, we compared transcriptional profiles freshly purified microglia, spleen using Affymetrix Mouse Genome arrays to identify genes predominantly expressed by microglia. Among tens thousands assayed, 127 potential candidates were found, including nine newly discovered encoding...
The nervous system is constantly infiltrated by blood-derived sentinels known as perivascular macrophages. Their immediate precursors have not yet been identified in situ and the mechanism that governs their recruitment mostly unknown. Here, we provide evidence CD68 + GR1 − monocytes can give rise to macrophages mice suffering from endotoxemia. After adhesion endothelium, these start crawl, adopt a rod-shaped morphology when passing through capillaries, manifest ability proliferate form long...
Abstract Recent findings implicate macrophages and some of their secreted products, especially tumor necrosis factor (TNF), as promoters. Inhibitors these inflammatory components are currently regarded potential therapeutic tools to block progression. Here, we show that infiltrating represented a significant population nonneoplastic cells within malignant gliomas, in which they were the exclusive producers TNF. Contrary reported pro-oncogenic effects TNF other types solid tumors,...
Neutrophils contribute to demyelinating autoimmune diseases, yet their phenotype and functions have been elusive date. Here, we demonstrate that ICAM1 surface expression distinguishes extra- from intravascular neutrophils in the mouse CNS during experimental encephalomyelitis (EAE). Transcriptomic analysis of these 2 subpopulations indicated neutrophils, once extravasated, acquire macrophage-like properties, including potential for immunostimulation MHC class II-mediated antigen...
Objective Nucleotides are danger signals that activate inflammatory responses via binding P2 receptors. The nucleoside triphosphate diphosphohydrolase-8 (NTPDase8) is an ectonucleotidase hydrolyses receptor ligands. We investigated the role of NTPDase8 in intestinal inflammation. Design generated NTPDase8-deficient ( Entpd8 –/– ) mice to define dextran sodium sulfate (DSS) colitis model. To assess inflammation, colons were collected and analysed by histopathology, reverse...
Microglia participate in the immune response upon central nervous system (CNS) infections. However, role of these cells during herpes simplex encephalitis (HSE) has not been fully characterized. We sought to identify different microglia/microglia-like and describe potential mechanisms signaling pathways involved HSE.The transcriptional CD11b+ cells, including was investigated using single-cell RNA sequencing (scRNA-seq) on isolated from ventral posterolateral nucleus (VPL)-enriched thalamic...
Neurodegenerative disorders refer to a group of diseases commonly associated with abnormal protein accumulation and aggregation in the central nervous system. However, exact role pathophysiology these remains unclear. This gap knowledge is due lack experimental models that allow for spatiotemporal control aggregation, investigation early dynamic events inclusion formation. Here, we report on development light-inducible (LIPA) system enables α-synuclein (α-syn) into insoluble deposits called...
Abstract Activation of microglia, the primary immune effectors CNS and proinflammatory signaling, is a hallmark brain damage. However, it remains controversial whether microglial cells have beneficial or detrimental functions in various neuropathological conditions. We report generation transgenic mice that express mutant form herpes simplex virus type 1 thymidine kinase (HSV‐1 TK mt‐30 ) driven by myeloid‐specific CD11b promoter. Using two paradigms nervous system damage, hypoglossal nerve...
Abstract Cytokine-inducible proteins named as suppressors of cytokine signaling (SOCS) are rapidly induced by interleukin-6 (IL-6) and other members sharing the gp130 receptor subunit after activation Janus kinases (JAK) signal transducers activators transcription (STAT). These inhibitory generally prevent tyrosine phosphorylation IL-6 gp130, specific JAK STAT or in acting at steps distal to activation. Expression these is therefore a useful tool investigate events occurring brain during...