A5016205291- Axon Guidance and Neuronal Signaling
- Neurogenesis and neuroplasticity mechanisms
- Nerve injury and regeneration
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Angiogenesis and VEGF in Cancer
- MicroRNA in disease regulation
- Hedgehog Signaling Pathway Studies
- Cellular Mechanics and Interactions
- Nanofabrication and Lithography Techniques
- 3D Printing in Biomedical Research
- Multiple Sclerosis Research Studies
- Sphingolipid Metabolism and Signaling
- Immune cells in cancer
- Hippo pathway signaling and YAP/TAZ
- RNA Research and Splicing
- Protein Tyrosine Phosphatases
- Growth Hormone and Insulin-like Growth Factors
- interferon and immune responses
- Cell Image Analysis Techniques
- Developmental Biology and Gene Regulation
- Circular RNAs in diseases
- Neuroscience and Neural Engineering
- RNA regulation and disease
- Apelin-related biomedical research
Montreal Neurological Institute and Hospital
2016-2025
McGill University
2016-2025
Rutgers, The State University of New Jersey
2022-2024
Rutgers Cancer Institute of New Jersey
2022-2024
Johnson University
2022-2024
Abilene Christian University
2024
Natural Sciences and Engineering Research Council
2018-2019
Génome Québec
2017
Robarts Clinical Trials
2014
The Neurological Institute
2013
Abstract Objective FTY720, a sphingosine‐1‐phosphate (S1P) receptor agonist that crosses the blood–brain barrier, is potential immuno‐therapy for multiple sclerosis. Our objective was to assess effect of FTY720 on process extension, differentiation, and survival human oligodendrocyte progenitor cells (OPCs), link functional effects with S1P expression signaling. Methods Functional assays studies were conducted A2B5+ OPCs derived from fetal central nervous system. Cells treated...
Seizure causes neuronal cell loss in both animal models and human epilepsy. To determine the contribution of apoptotic mechanisms to seizure-induced death, rat brains were examined for occurrence terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL)-positive nuclei after pilocarpine-induced seizure. Numerous TUNEL-positive cells observed throughout postseizure hippocampus, piriform cortex, entorhinal cortex. Combined TUNEL/NeuN immunocytochemistry demonstrated that...
ABSTRACT An intermediate target for axons leaving the cerebral cortex in embryonic mammals is ganglionic eminence (GE), precursor of basal ganglia. The cues that direct these over initial portion their trajectory are not well understood, but could include both short-range and long-range attractants repellents. In present study, we provide evidence corticofugal might be guided at least partly by a diffusible factor or factors originating lateral GE sulcus between medial ridges (ISS), as...
The thalamocortical axon (TCA) projection originates in dorsal thalamus, conveys sensory input to the neocortex, and has a critical role cortical development. We show that secreted guidance molecule netrin-1 acts vitro as an attractant growth promoter for thalamic axons is required proper development of TCA vivo . As TCAs approach hypothalamus, they turn laterally into ventral telencephalon extend toward cortex through population -expressing cells. DCC neogenin , receptors implicated...
Gradients of diffusible long-range attractant and repellent proteins have been proposed to guide growing axons during nervous system development, but such gradients never visualized directly. In the embryonic spinal cord, commissural pioneer a circumferential trajectory floor plate at ventral midline directed by secreted netrin family. chick cord netrin-1 mRNA is expressed cells netrin-2 neural epithelial cells. Antibodies two netrins reveal gradient protein directly in path axons. The...
Extracellular cues direct axon extension by regulating growth cone morphology. The netrin-1 receptor deleted in colorectal cancer (DCC) is required for commissural to the floor plate embryonic spinal cord. Here we demonstrate that challenging rat neurons with netrin-1, either solution or as a substrate, causes DCC-dependent increases surface area and filopodia number, which term expansion. We provide evidence DCC influences morphology at least two mechanisms. First, mediates an adhesive...
Blood–brain barrier function is driven by the influence of astrocyte-secreted factors. During neuroinflammatory responses blood–brain compromised resulting in central nervous system damage and exacerbated pathology. Here, we identified endothelial netrin 1 induction as a vascular response to astrocyte-derived sonic hedgehog that promotes autocrine properties during homeostasis increases with inflammation. Netrin supports integrity upregulating junctional protein expression, while knockout...
Fingolimod (FTY720) and its phosphorylated form FTY720P are modulators of sphingosine-1-phosphate (S1P) receptors, which G-protein coupled receptors linked to cell migration vascular maturation. The efficacy FTY720 in autoimmune diseases such as multiple sclerosis animal models has been attributed inhibition lymphocyte trafficking target organs. In this study, we examined the role S1P cultured rat oligodendrocytes (OLGs) OLG progenitor cells (OPCs) using active FTY720. We found that (1)...
The transmembrane protein deleted in colorectal cancer (DCC) and its ligand, netrin-1, regulate synaptogenesis during development, but their function the mature central nervous system is unknown. Given that DCC promotes cell-cell adhesion, expressed by neurons, activates proteins signal at synapses, we hypothesized expression neurons regulates synaptic plasticity adult brain. We report enriched dendritic spines of pyramidal wild-type mice, demonstrate selective deletion from forebrain...
Remyelination of lesions in the central nervous system contributes to neural repair following clinical relapses multiple sclerosis. is initiated by recruitment and differentiation oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes. Simvastatin, a blood-brain barrier-permeable statin sclerosis trials, has been shown impact vitro processes that have implicated remyelination. Animals were fed cuprizone-supplemented diet for 6 weeks induce localized demyelination corpus...
Netrin-1 is a secreted protein that directs long-range axon guidance during early stages of neural circuit formation and continues to be expressed in the mammalian forebrain postnatal period peak synapse formation. Here we demonstrate synaptogenic function netrin-1 rat mouse cortical neurons investigate underlying mechanism. We report its receptor DCC are widely by developing cortex enriched at synapses vivo . detect distributed along axons dendrites cultured provide evidence newly...
Multiple sclerosis (MS) lesions feature demyelination with limited remyelination. A distinct injury phenotype of MS features dying back oligodendrocyte (OL) terminal processes, a response that destabilizes myelin/axon interactions. This oligodendrogliopathy has been linked local metabolic stress, similar to the penumbra ischemic/hypoxic states. Here, we developed an in vitro model using human CNS-derived OLs and related this their bioenergetic properties. We determined energy utilization...
The mouse monoclonal antibody marketed as anti-adenomatous polyposis coli clone CC1, often referred to is the most commonly used specifically label mature oligodendrocytes without labeling myelin. Previous studies have shown that despite being raised against adenomatous coli, this binds another unknown antigen. We show CC1 Quaking 7, an RNA-binding protein highly up-regulated in myelinating central nervous system. (APC) cell bodies of oligodendrocytes. Despite APC, previous showed (QKI) which
Netrin-1 regulates cell migration and adhesion during the development of nervous system, vasculature, lung, pancreas, muscle, mammary gland. It is also proposed to function as a dependence ligand that inhibits apoptosis; however, studies disagree regarding whether netrin-1 loss-of-function mice exhibit increased death. Furthermore, previously studied gene-trap express netrin-1-β-galactosidase protein chimera with potential for toxic gain-of-function effects, well small amount wild-type...
Netrins are a family of secreted proteins that function as chemotropic axon guidance cues during neural development. Here we demonstrate netrin-1 continues to be expressed in the adult rat spinal cord at level similar embryonic CNS. In contrast, netrin-3, which is also cord, was not detected adult. situ hybridization analysis demonstrated cells white matter and gray express netrin-1. Colocalization studies using neuronal marker NeuN revealed by multiple classes interneurons motoneurons....