title: Increased p75 neurotrophin receptor expression in the canine distemper virus model of multiple sclerosis identifies aldynoglial Schwann cells that emerge in response to axonal damage.
abstract: Gliogenesis under pathophysiological conditions is of particular clinical relevance since it may provide regeneration-promoting cells recruitable for therapeutic purposes. There is accumulating evidence that aldynoglial cells with Schwann cell-like growth-promoting properties emerge in the lesioned CNS. However, the characterization of these cells and the signals triggering their in situ generation have remained enigmatic. In the present study, we used the p75 neurotrophin receptor (p75(NTR) ) as a marker for Schwann cells to study gliogenesis in the well-defined canine distemper virus (CDV)-induced demyelination model. White matter lesions of CDV-infected dogs contained bi- to multipolar, p75(NTR) -expressing cells that neither expressed MBP, GFAP, BS-1, or P0 identifying oligodendroglia, astrocytes, microglia, and myelinating Schwann cells nor CDV antigen. Interestingly, p75(NTR) -expression became apparent prior to the onset of demyelination in parallel to the expression of β-amyloid precursor protein (β-APP), nonphosphorylated neurofilament (n-NF), BS-1, and CD3, and peaked in subacute lesions with inflammation. To study the role of infiltrating immune cells during differentiation of Schwann cell-like glia, organotypic slice cultures from the normal olfactory bulb were established. Despite the absence of infiltrating lymphocytes and macrophages, a massive appearance of p75(NTR) -positive Schwann-like cells and BS-1-positive microglia was noticed at 10 days in vitro. It is concluded that axonal damage as an early signal triggers the differentiation of tissue-resident precursor cells into p75(NTR) -expressing aldynoglial Schwann cells that retain an immature pre-myelin state. Further studies have to address the role of microglia during this process and the regenerative potential of aldynoglial cells in CDV infection and other demyelinating diseases.
authors.affiliation: Department of Pathology, University of Veterinary Medicine, Bünteweg 17, D-30559 Hannover, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Imbschweiler
authors.forename: Frauke
authors.initials: F
authors.lastname: Seehusen
authors.forename: Claas-Tido
authors.initials: CT
authors.lastname: Peck
authors.forename: Mohamed
authors.initials: M
authors.lastname: Omar
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumgärtner
authors.forename: Konstantin
authors.initials: K
authors.lastname: Wewetzer
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D004195:Disease Models, Animal; D004216:Distemper / Q000150:complications*; D004217:Distemper Virus, Canine / Q000472:pathogenicity; D004285:Dogs; D000431:Ethanol / Q000031:analogs & derivatives / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D009103:Multiple Sclerosis / Q000209:etiology* / Q000473:pathology* / Q000821:virology; D009830:Olfactory Bulb / Q000473:pathology / Q000821:virology; D009836:Oligodendroglia / Q000378:metabolism*; D009924:Organ Culture Techniques; D020800:Receptor, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology; D013440:Sulfides / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D020800:Receptor, Nerve Growth Factor; D013440:Sulfides; D014764:Viral Proteins; D000431:Ethanol; C077818:bis(2-hydroxyethyl)trisulfide