Stiftung Tierärztliche Hochschule Hannover (TiHo)

Neurotoxic potential of reactive astrocytes in canine distemper demyelinating leukoencephalitis

Affiliation
Department of Pathology, University of Veterinary Medicine Hanover, Hannover, Germany.
Klemens, J;
ORCID
0000-0001-6277-7366
Affiliation
Department of Pathology, University of Veterinary Medicine Hanover, Hannover, Germany.
Ciurkiewicz, M;
Affiliation
Department of Pathology, University of Veterinary Medicine Hanover, Hannover, Germany.
Chludzinski, E;
ORCID
0000-0002-8046-4731
Affiliation
Department of Pathology, University of Veterinary Medicine Hanover, Hannover, Germany.
Iseringhausen, Martin;
Affiliation
Department of Pathology, University of Veterinary Medicine Hanover, Hannover, Germany.
Klotz, D;
Affiliation
Department of Pathology, University of Veterinary Medicine Hanover, Hannover, Germany.
Pfankuche, V M;
Affiliation
Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald, Insel Riems, Germany.
Ulrich, R;
Affiliation
Department of Pathology, University of Veterinary Medicine Hanover, Hannover, Germany.
Herder, V;
Affiliation
Department of Pathology, University of Veterinary Medicine Hanover, Hannover, Germany.
Puff, C;
GND
142929565
ORCID
0000-0001-8151-5644
Affiliation
Department of Pathology, University of Veterinary Medicine Hanover, Hannover, Germany.
Baumgärtner, Wolfgang;
ORCID
0000-0003-2187-3436
Affiliation
Department of Pathology, University of Veterinary Medicine Hanover, Hannover, Germany. andreas.beineke@tiho-hannover.de.
Beineke, Andreas

Canine distemper virus (CDV) causes a fatal demyelinating leukoencephalitis in young dogs resembling human multiple sclerosis. Astrocytes are the main cellular target of CDV and undergo reactive changes already in pre-demyelinating brain lesions. Based on their broad range of beneficial and detrimental effects in the injured brain reactive astrogliosis is in need of intensive investigation. The aim of the study was to characterize astrocyte plasticity during the course of CDV-induced demyelinating leukoencephalitis by the aid of immunohistochemistry, immunofluorescence and gene expression analysis. Immunohistochemistry revealed the presence of reactive glial fibrillary acidic protein (GFAP)+ astrocytes with increased survivin and reduced aquaporin 4, and glutamine synthetase protein levels, indicating disturbed blood brain barrier function, glutamate homeostasis and astrocyte maladaptation, respectively. Gene expression analysis revealed 81 differentially expressed astrocyte-related genes with a dominance of genes associated with neurotoxic A1-polarized astrocytes. Accordingly, acyl-coA synthetase long-chain family member 5+/GFAP+, and serglycin+/GFAP+ cells, characteristic of A1-astrocytes, were found in demyelinating lesions by immunofluorescence. In addition, gene expression revealed a dysregulation of astrocytic function including disturbed glutamate homeostasis and altered immune function. Observed findings indicate an astrocyte polarization towards a neurotoxic phenotype likely contributing to lesion initiation and progression in canine distemper leukoencephalitis.

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