Oligodendroglial degeneration in distemper: apoptosis or necrosis?
Canine distemper virus (CDV) causes a multifocal demyelinating disease in dogs. It was previously shown that the initial demyelinating lesions are directly virus induced since a correlation between the occurrence of demyelination and CDV replication in white matter cells was observed. During the course of infection oligodendrocytes undergo distinct morphological alterations, partly due to a restricted CDV infection of these cells, and eventually disappear from the lesions. This phenomenon has been described in vivo as well as in vitro. However, the reason for the morphological alterations and the following oligodendroglial depletion remained unclear. Since virus infection can induce cell death, it was investigated whether apoptosis or necrosis plays a role in the pathogenesis of demyelination in canine distemper. In brain tissue sections from dogs with acute distemper apoptotic cells were not detected within the demyelinating lesions using morphological and biochemical cell death criteria. In chronic distemper, apoptotic cells - presumably inflammatory cells - were seen within the perivascular cuffs. These in vivo findings were correlated to the in vitro situation using CDV-infected primary dog brain cell cultures as well as Vero cells. Infection with culture-adapted CDV lead to massive necrosis but not to apoptosis. After infection with virulent CDV neither apoptosis nor necrosis was a predominant feature in either culture system. These findings suggest that virus-induced demyelination in canine distemper is not the direct consequence of apoptosis or necrosis. It is speculated that another mechanism must be responsible for the observed morphological alterations of oligodendrocytes, ultimately leading to demyelination.
Schobesberger
M
M
Institute of Animal Neurology, University of Berne, Switzerland.
Zurbriggen
A
A
Summerfield
A
A
Vandevelde
M
M
Griot
C
C
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000473:pathology; D048429:Cell Size; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003711:Demyelinating Diseases / Q000473:pathology; D004216:Distemper / Q000473:pathology*; D004285:Dogs; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D009336:Necrosis; D009836:Oligodendroglia / Q000473:pathology*; D013997:Time Factors; D014709:Vero Cells