title: Neuronopathy in the motor neocortex in a chronic model of multiple sclerosis.
abstract: We provide evidence of cortical neuronopathy in myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis, an established model of chronic multiple sclerosis. To investigate phenotypic perturbations in neurons in this model, we used apoptotic markers and immunohistochemistry with antibodies to NeuN and other surrogate markers known to be expressed by adult pyramidal Layer V somas, including annexin V, encephalopsin, and Emx1. We found no consistent evidence of chronic loss of Layer V neurons but detected both reversible and chronic decreases in the expression of these markers in conjunction with evidence of cortical demyelination and presynaptic loss. These phenotypic perturbations were present in, but not restricted to, the neocortical Layer V. We also investigated inflammatory responses in the cortex and subcortical white matter of the corpus callosum and spinal dorsal funiculus and found that those in the cortex and corpus callosum were delayed compared with those in the spinal cord. Inflammatory infiltrates initially included T cells, neutrophils, and Iba1-positive microglia/macrophages in the corpus callosum, whereas only Iba1-positive cells were present in the cortex. These data indicate that we have identified a new temporal pattern of subtle phenotypic perturbations in neocortical neurons in this chronic multiple sclerosis model.
authors.affiliation: From the Department of Neurology, University of California Davis, Sacramento (TB, LM, JX, MM, DP); Department of Biomedical Engineering, University of California Davis, Davis (AM); Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, Sacramento (MM, DP, PB); and Department of Cell Biology and Human Anatomy, University of California Davis, Davis (PB), California.
authors.forename: Travis
authors.initials: T
authors.lastname: Burns
authors.forename: Laird
authors.initials: L
authors.lastname: Miers
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Alan
authors.initials: A
authors.lastname: Man
authors.forename: Monica
authors.initials: M
authors.lastname: Moreno
authors.forename: David
authors.initials: D
authors.lastname: Pleasure
authors.forename: Peter
authors.initials: P
authors.lastname: Bannerman
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology; D005620:Freund's Adjuvant / Q000633:toxicity; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology*; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D004676:Myelin Basic Protein / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D019579:Neocortex / Q000187:drug effects / Q000473:pathology*; D010446:Peptide Fragments / Q000633:toxicity; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors
chemical_list: D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D016708:Synaptophysin; C445081:myelin oligodendrocyte glycoprotein (35-55); D005620:Freund's Adjuvant; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase