title: Differential expression of sonic hedgehog immunoreactivity during lesion evolution in autoimmune encephalomyelitis.
abstract: The signaling molecule Sonic hedgehog (Shh) is involved in several processes of central nervous system development. Recent reports indicate that Shh expression plays a role also in certain pathologic conditions in the adult brain, including multiple sclerosis and its animal model. However, the role of Shh signaling in immune-mediated demyelinating disease remains still uncertain. The aim of our study was to investigate the distribution pattern of Shh immunoreactivity (Shh-IR) during lesion evolution in myelin-oligodendrocyte-glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE), a model strongly mimicking multiple sclerosis. MOG-EAE was actively induced in DA rats. Histologic evaluation was performed with light and confocal microscopy on paraffin-embedded central nervous system sections from days 20 to 120 after active immunization. Shh-IR was present within the lesions of MOG-EAE during all stages of lesion evolution. The highest staining intensity for Shh was found in remyelinating lesions. In actively demyelinating, inactive demyelinated lesions, and in remyelinating lesions, Shh-IR was detected in macrophages, endothelium, and astrocytes. Shh-IR in axons was exclusively present in remyelinating lesions. Although the exact molecular mechanisms of the Shh-signaling pathway in experimental autoimmune encephalomyelitis are yet to be determined, our findings may imply a role of Shh signaling in facilitating remyelination.
authors.affiliation: Department of Neurology, Medical University Graz, Graz, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Seifert
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.forename: Robert
authors.initials: R
authors.lastname: Weissert
authors.forename: Franz
authors.initials: F
authors.lastname: Fazekas
authors.forename: Maria K
authors.initials: MK
authors.lastname: Storch
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002452:Cell Count / Q000379:methods; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D053823:Hedgehog Proteins; D018613:Microscopy, Confocal / Q000379:methods; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009444:Neuritis, Autoimmune, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D016900:Neurofilament Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D051381:Rats; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D053823:Hedgehog Proteins; C571328:Mog protein, rat; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D016900:Neurofilament Proteins; D015534:Trans-Activators; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases