Activation of microglia cells is dispensable for the induction of rat retroviral spongiform encephalopathy

• Published in: Journal of neurovirology Vol. 7; no. 6; pp. 501 - 510
• Main Author: Hansen, Christian Sauder, Stefanie Czub, Eva Bachmann, Simone Schimmer, Annette Hegyi, Markus Czub, Regine
• Format: Journal Article
• Language: English
• Published: United States Informa UK Ltd 01-12-2001
• Subjects: Animals; Cerebral Cortex - immunology; Encephalitis, Viral - immunology; Encephalitis, Viral - pathology; Encephalitis, Viral - virology; Gene Expression - immunology; Immunohistochemistry; Interleukin-1 - genetics; Interleukin-1 - immunology; Interleukin-6 - genetics; Interleukin-6 - immunology; Leukemia Virus, Murine; Microglia - immunology; Microglia - virology; Murine leukemia virus; Neurodegenerative Diseases - immunology; Neurodegenerative Diseases - pathology; Neurodegenerative Diseases - virology; Rats; Rats, Inbred F344; Retroviridae Infections - immunology; Retroviridae Infections - pathology; RNA, Messenger - analysis; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Viral Envelope Proteins - analysis; Viral Envelope Proteins - immunology
• ISSN: 1355-0284; 1538-2443
• DOI: 10.1080/135502801753248088

In the course of retroviral CNS infections, microglia activation has been observed frequently, and it has been hypothesized that activated microglia produce and secrete neurotoxic products like proinflammatory cytokines, by this promoting brain damage. We challenged this hypothesis in a rat model for neurodegeneration. In a kinetic study, we found that microglia cells of rats neonatally inoculated with neurovirulent murine leukemia virus (MuLV) NT40 became infected in vivo to maximal levels within 9-13 days postinoculation (d.p.i.). Beginning from 13 d.p.i., degenerative alterations, i.e., vacuolization of neurons and neuropil were found in cerebellar and other brain-stem nuclei. Elevated numbers of activated microglia cells—as revealed by immuno-histochemical staining with monoclonal antibody ED1—were first detected at 19 d.p.i. and were always locally associated with degenerated areas but not with nonaltered, yet infected, brain regions. Both neuropathological changes and activated microglia cells increased in intensity and numbers, respectively, with ongoing infection but did not spread to other than initially affected brain regions. By ribonuclease protection assays, we were unable to detect differences in the expression levels of tumor-necrosis-factor- &#102 (TNF- &#102 ), interleukin1 &#103 (IL-1 &#103 ), and interleukin-6 (IL-6) in microglia cells nor in total brains from infected versus uninfected rats. Our results suggest that the activation of microglia in the course of MuLV neurodegeneration is rather a reaction to, and not the cause of, neuronal damage. Furthermore, overt expression of the proinflammatory cytokines TNF- &#102 , IL-1 &#103 , and IL-6 within the CNS is not required for the induction of retroviral associated neurodegeneration in rats.