scholarly journals MicroRNA-223 protects neurons from degeneration in experimental autoimmune encephalomyelitis

Brain ◽  
2019 ◽  
Vol 142 (10) ◽  
pp. 2979-2995 ◽  
Author(s):  
Barbara Morquette ◽  
Camille A Juźwik ◽  
Sienna S Drake ◽  
Marc Charabati ◽  
Yang Zhang ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Neurodegenerative Diseases ◽  
Glutamate Receptor ◽  
Therapeutic Potential ◽  
Axonal Damage ◽  
Rodent Model ◽  
Autoimmune Encephalomyelitis ◽  
Receptor Signalling ◽  
Experimental Autoimmune

Dysregulation of miRNAs has been observed in many neurodegenerative diseases, including multiple sclerosis. Morquette et al. show that overexpression of miR-223-3p prevents accumulation of axonal damage in a rodent model of multiple sclerosis, in part through regulation of glutamate receptor signalling. Manipulation of miRNA levels may have therapeutic potential.

scholarly journals Cyclophilin D inactivation protects axons in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis

2007 ◽  
Vol 104 (18) ◽  
pp. 7558-7563 ◽  
Author(s):  
Michael Forte ◽  
Bruce G. Gold ◽  
Gail Marracci ◽  
Priya Chaudhary ◽  
Emy Basso ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Molecular Mechanisms ◽  
Mitochondrial Permeability Transition ◽  
Neurodegenerative Disorder ◽  
Axonal Damage ◽  
Inflammatory Disorder ◽  
Cyclophilin D ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is the leading cause of neurological disability in young adults, affecting some two million people worldwide. Traditionally, MS has been considered a chronic, inflammatory disorder of the central white matter in which ensuing demyelination results in physical disability [Frohman EM, Racke MK, Raine CS (2006) N Engl J Med 354:942–955]. More recently, MS has become increasingly viewed as a neurodegenerative disorder in which neuronal loss, axonal injury, and atrophy of the CNS lead to permanent neurological and clinical disability. Although axonal pathology and loss in MS has been recognized for >100 years, very little is known about the underlying molecular mechanisms. Progressive axonal loss in MS may stem from a cascade of ionic imbalances initiated by inflammation, leading to mitochondrial dysfunction and energetic deficits that result in mitochondrial and cellular Ca2+ overload. In a murine disease model, experimental autoimmune encephalomyelitis (EAE) mice lacking cyclophilin D (CyPD), a key regulator of the mitochondrial permeability transition pore (PTP), developed EAE, but unlike WT mice, they partially recovered. Examination of the spinal cords of CyPD-knockout mice revealed a striking preservation of axons, despite a similar extent of inflammation. Furthermore, neurons prepared from CyPD-knockout animals were resistant to reactive oxygen and nitrogen species thought to mediate axonal damage in EAE and MS, and brain mitochondria lacking CyPD sequestered substantially higher levels of Ca2+. Our results directly implicate pathological activation of the mitochondrial PTP in the axonal damage occurring during MS and identify CyPD, as well as the PTP, as a potential target for MS neuroprotective therapies.

scholarly journals Focal and diffuse cortical degenerative changes in a marmoset model of multiple sclerosis

2010 ◽  
Vol 16 (5) ◽  
pp. 537-548 ◽  
Author(s):  
IM Pomeroy ◽  
EK Jordan ◽  
JA Frank ◽  
PM Matthews ◽  
MM Esiri
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Grey Matter ◽  
Neuronal Loss ◽  
Axonal Damage ◽  
Inflammatory Factors ◽  
Focal Lesions ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Background: Degenerative features, such as neuronal, glial, synaptic and axonal loss, have been identified in neocortical and other grey matter structures in patients with multiple sclerosis, but mechanisms for neurodegeneration are unclear. Cortical demyelinating lesions are a potential cause of this degeneration, but the pathological and clinical significance of these lesions is uncertain as they remain difficult to identify and study in vivo. In this study we aimed to describe and quantify cellular and subcellular pathology in the cortex of myelin oligodendrocyte glycoprotein-induced marmoset experimental autoimmune encephalomyelitis using quantitative immunohistochemical methods. Results: We found evidence of diffuse axonal damage occurring throughout cortical grey matter with evidence for synaptic loss and gliosis and a 13.6% decrease in neuronal size and occurring in deep cortical layers. Evidence of additional axonal damage and a 29.6—36.5% loss of oligodendrocytes was found in demyelinated cortical lesions. Leucocortical lesions also showed neuronal loss of 22.2% and a 15.8% increase in oligodendrocyte size. Conclusions: The marmoset experimental autoimmune encephalomyelitis model, therefore, shows both focal and generalized neurodegeneration. The generalized changes cannot be directly related to focal lesions, suggesting that they are either a consequence of diffusible inflammatory factors or secondary to remote lesions acting through trans-synaptic or retrograde degeneration.

scholarly journals Axonal damage in spinal cord is associated with gray matter atrophy in sensorimotor cortex in experimental autoimmune encephalomyelitis

2019 ◽  
Vol 26 (3) ◽  
pp. 294-303 ◽  
Author(s):  
Cassandra E Meyer ◽  
Josephine L Gao ◽  
James Ying-Jie Cheng ◽  
Mandavi R Oberoi ◽  
Hadley Johnsonbaugh ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Gray Matter ◽  
Sensorimotor Cortex ◽  
Axonal Damage ◽  
Strongly Correlated ◽  
Autoimmune Encephalomyelitis ◽  
Normal Controls ◽  
Experimental Autoimmune

Background: Gray matter (GM) atrophy in brain is one of the best predictors of long-term disability in multiple sclerosis (MS), and recent findings have revealed that localized GM atrophy is associated with clinical disabilities. GM atrophy associated with each disability mapped to a distinct brain region, revealing a disability-specific atlas (DSA) of GM loss. Objective: To uncover the mechanisms underlying the development of localized GM atrophy. Methods: We used voxel-based morphometry (VBM) to evaluate localized GM atrophy and Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging-compatible Tissue-hYdrogel (CLARITY) to evaluate specific pathologies in mice with experimental autoimmune encephalomyelitis (EAE). Results: We observed extensive GM atrophy throughout the cerebral cortex, with additional foci in the thalamus and caudoputamen, in mice with EAE compared to normal controls. Next, we generated pathology-specific atlases (PSAs), voxelwise mappings of the correlation between specific pathologies and localized GM atrophy. Interestingly, axonal damage (end-bulbs and ovoids) in the spinal cord strongly correlated with GM atrophy in the sensorimotor cortex of the brain. Conclusion: The combination of VBM with CLARITY in EAE can localize GM atrophy in brain that is associated with a specific pathology in spinal cord, revealing a PSA of GM loss.

A novel connection of autophagy related gene 7 to multiple sclerosis and experimental autoimmune encephalomyelitis

2014 ◽  
Vol 275 (1-2) ◽  
pp. 136-137
Author(s):  
Rasmus Berglund ◽  
Melanie Thessen Hedreul ◽  
Roham Parsa ◽  
Petra Bergman ◽  
Maja Jagodic ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Related Gene ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune
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