title: Accumulation of Extracellular Matrix in Advanced Lesions of Canine Distemper Demyelinating Encephalitis.
abstract: In demyelinating diseases, changes in the quality and quantity of the extracellular matrix (ECM) may contribute to demyelination and failure of myelin repair and axonal sprouting, especially in chronic lesions. To characterize changes in the ECM in canine distemper demyelinating leukoencephalitis (DL), histochemical and immunohistochemical investigations of formalin-fixed paraffin-embedded cerebella using azan, picrosirius red and Gomori`s silver stain as well as antibodies directed against aggrecan, type I and IV collagen, fibronectin, laminin and phosphacan showed alterations of the ECM in CDV-infected dogs. A significantly increased amount of aggrecan was detected in early and late white matter lesions. In addition, the positive signal for collagens I and IV as well as fibronectin was significantly increased in late lesions. Conversely, the expression of phosphacan was significantly decreased in early and more pronounced in late lesions compared to controls. Furthermore, a set of genes involved in ECM was extracted from a publically available microarray data set and was analyzed for differential gene expression. Gene expression of ECM molecules, their biosynthesis pathways, and pro-fibrotic factors was mildly up-regulated whereas expression of matrix remodeling enzymes was up-regulated to a relatively higher extent. Summarized, the observed findings indicate that changes in the quality and content of ECM molecules represent important, mainly post-transcriptional features in advanced canine distemper lesions. Considering the insufficiency of morphological regeneration in chronic distemper lesions, the accumulated ECM seems to play a crucial role upon regenerative processes and may explain the relatively small regenerative potential in late stages of this disease.
authors.affiliation: Department of Pathology, University of Veterinary Medicine, Hannover, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Seehusen
authors.affiliation: Department of Pathology, University of Veterinary Medicine, Hannover, Germany.
authors.forename: Seham A
authors.initials: SA
authors.lastname: Al-Azreg
authors.affiliation: Department of Pathology, University of Veterinary Medicine, Hannover, Germany.
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Raddatz
authors.affiliation: Department of Pathology, University of Veterinary Medicine, Hannover, Germany.|Boehringer Ingelheim Veterinary Research Center GmbH & Co. KG, Hannover, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Haist
authors.affiliation: Department of Pathology, University of Veterinary Medicine, Hannover, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Puff
authors.affiliation: Department of Pathology, University of Veterinary Medicine, Hannover, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Spitzbarth
authors.affiliation: Department of Pathology, University of Veterinary Medicine, Hannover, Germany.|Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald - Insel Riems, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Ulrich
authors.affiliation: Department of Pathology, University of Veterinary Medicine, Hannover, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumgärtner
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D003711:Demyelinating Diseases / Q000662:veterinary*; D018450:Disease Progression; D004216:Distemper / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D004217:Distemper Virus, Canine; D004285:Dogs; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry
chemical_list: D016326:Extracellular Matrix Proteins