TopicNeuroscience

demyelination

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28Total items

26ePosters

2Seminars

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SeminarNeuroscience

The role of CNS microglia in health and disease

Kyrargyri Vassiliki

Department of Immunology, Laboratory of Molecular Genetics, Hellenic Pasteur Institute, Athens, Greece

Oct 25, 2023

Microglia are the resident CNS macrophages of the brain parenchyma. They have many and opposing roles in health and disease, ranging from inflammatory to anti-inflammatory and protective functions, depending on the developmental stage and the disease context. In Multiple Sclerosis, microglia are involved to important hallmarks of the disease, such as inflammation, demyelination, axonal damage and remyelination, however the exact mechanisms controlling their transformation towards a protective or devastating phenotype during the disease progression remains largely unknown until now. We wish to understand how brain microglia respond to demyelinating insults and how their behaviour changes in recovery. To do so we developed a novel histopathological analysis approach in 3D and a cell-based analysis tool that when applied in the cuprizone model of demyelination revealed region- and disease- dependent changes in microglial dynamics in the brain grey matter during demyelination and remyelination. We now use similar approaches with the aim to unravel sensitive changes in microglial dynamics during neuroinflammation in the EAE model. Furthermore, we employ constitutive knockout and tamoxifen-inducible gene-targeting approaches, immunological techniques, genetics and bioinformatics and currently seek to clarify the specific role of the brain resident microglial NF-κB molecular pathway versus other tissue macrophages in EAE.

SeminarNeuroscience

The immunopathology of advanced multiple sclerosis

Inge Huitinga

Brain Bank

Oct 19, 2020

We recently analyzed a large cohort of multiple sclerosis (MS) autopsy cases of the Netherlands Brain Bank (NBB) and showed that 57% of the lesion in advanced MS is active (containing activated microglia/macrophages). These active lesions correlated with disease severity and differed between males and female MS patients.1 Already in normal appearing white matter microglia show early signs of demyelination.5 T cells are also frequently present in advanced stages of MS and have a tissue resident memory (Trm) phenotype, are more frequently CD8+ then CD4+, are located perivascular, enriched in active and mixed active/inactive MS lesions and correlated with lesion activity, lesion load and disease severity.2-4 Like Trm cells, B cells are located perivascular and were also enriched in active MS lesions but in lower numbers and a proportion of the MS patients had almost no detectable B cells in the regions analyzed. MS patients with limited presence of B cells had less severe MS, and less active and mixed active /inactive lesions. We conclude that advanced MS is characterize by a high innate and adaptive immune activity which is heterogeneous and relates to the clinical disease course.

demyelination

Latest

The role of CNS microglia in health and disease

The immunopathology of advanced multiple sclerosis

EARLY DEMYELINATION OF THE HIPPOCAMPAL COMMISSURE DRIVES FUNCTIONAL NETWORK DISINTEGRATION BEFORE OVERT NEURODEGENERATION IN ALZHEIMER’S DISEASE

INVESTIGATION OF THE REGENERATIVE POTENTIAL OF PROTEOGLYCAN 4A IN THE BRAIN IN ZEBRAFISH MODELS OF TRAUMATIC BRAIN INJURY AND DEMYELINATION

MITOCHONDRIAL DYNAMICS ARE SELECTIVELY ALTERED IN PARVALBUMIN NEURONS DURING GREY MATTER DEMYELINATION

ROLE OF ADENOSINE A2B RECEPTOR AGONISM AND ANTAGONISM IN AN IN VIVO MOUSE MODEL OF SEVERE DEMYELINATION

NOVEL THERAPIES TO HALT DEMYELINATION IN PROGRESSIVE MULTIPLE SCLEROSIS

CELL-SPECIFIC REGULATION OF MIF DURING DEMYELINATION AND REMYELINATION

ROLE OF ADENOSINE A2B RECEPTORS DURING CUPRIZONE-INDUCED DEMYELINATION IN AN IN VIVO MOUSE MODEL

DISSECTING THE ROLE OF MICROGLIAL TDP-43 IN DEMYELINATION AND LIPID HANDLING

RELEVANCE OF VASCULAR ABNORMALITIES IN NEURODEGENERATIVE DEMYELINATION

RECOVERY OF LIPID PROFILE AFTER CUPRIZONE-INDUCED DEMYELINATION IN YOUNG AND MATURE C57BL/6 MICE

THE EFFECT OF OLIGODENDROGLIAL-ADAM10 DEFICIENCY UPON CHEMICAL- OR MECHANICAL-INDUCED CENTRAL NERVOUS SYSTEM DEMYELINATION IN MICE

EPSILON TOXIN–INDUCED DEMYELINATION IN THE MOUSE CORPUS CALLOSUM: IN VITRO AND IN VIVO EVIDENCE SUPPORTING A LINK TO MULTIPLE SCLEROSIS

CHARACTERIZATION OF THE ACUTE GENE RESPONSE IN ZEBRAFISH DEMYELINATION MODEL

Alterations in pacemaker channel’s modulations of thalamic relay neurons by demyelination due to CPZ treatment and neuroprotective effects of DRF

Demyelination of the fornix commissure as an early event in Alzheimer’s disease

Demyelination impairs layer 5 corticothalamic feedback in the somatosensory system

Identification of functional biomarkers of demyelination in two animal models of Multiple Sclerosis with functional Ultrasound Imaging

Immunocompetent cerebral spheroids as a model system to evaluate drug-mediated demyelination and to study remyelination

The prevalence and topography of demyelination and inflammatory activity in the multiple sclerosis spinal cord

Revisiting the role of androgens in demyelination models of the central nervous system

Cannabinoid CB1 receptors in oligodendrocytes: Modulation of energy metabolism and autoimmune demyelination

Elucidating the impact of demyelination and remyelination on inhibitory synaptic transmission in the somatosensory cortex of a mouse model of cuprizone

Longitudinal single-cell and brain transcriptomic characterization of microglia signatures during experimental demyelination and remyelination

Morphological and molecular characterization of cortical protoplasmic astrocytes during early experimental demyelination

Targeting PAC1 receptors to prevent CNS white matter inflammation, synapse loss, and locomotor deficits in the cuprizone demyelination model

The trial of small molecules to promote re-myelination and neuroprotection in an animal model of demyelination and neuroinflammation