Abstract
Ganciclovir is effective in the treatment of human infections with viruses of the Herpesviridae family. Beside antiviral properties, recently ganciclovir was described to inhibit microglial proliferation and disease severity of experimental autoimmune encephalomyelitis, an inflammatory model of multiple sclerosis. Microglial activation and proliferation are main characteristics of neuroinflammatory CNS diseases and inhibition of microglial functions might be beneficial in autoimmune diseases, or detrimental in infectious diseases. The objective of this study was to determine potential inhibitory effects of ganciclovir in three different murine animal models of CNS neuroinflammation in which microglia play an important role: Theiler´s murine encephalomyelitis, the cuprizone model of de- and remyelination, and the vesicular stomatitis virus encephalitis model. In addition, in vitro experiments with microglial cultures were performed to test the hypothesis that ganciclovir inhibits microglial proliferation. In all three animal models, neither microglial proliferation or recruitment nor disease activity was changed by ganciclovir. In vitro experiments confirmed that microglial proliferation was not affected by ganciclovir. In conclusion, our results show that the antiviral drug ganciclovir does not inhibit microglial activation and proliferation in the murine CNS.
Highlights
Of microglial functions might induce deleterious effects
We evaluated the effects of ganciclovir on microglia in Theilers murine encephalomyelitis (TME), the cuprizone model of de- and remyelination, and the vesicular stomatitis virus (VSV) encephalitis model
We found that TME virus (TMEV) infection is accompanied by prominent microglial proliferation and activation (Fig. 1E,F) as previously observed by others[16]
Summary
Of microglial functions might induce deleterious effects For this reason, the aim of the present study was to determine possible inhibitory effects of ganciclovir on microglia by using three different murine models of CNS neuroinflammation in which microglia play an important role. We evaluated the effects of ganciclovir on microglia in Theilers murine encephalomyelitis (TME), the cuprizone model of de- and remyelination, and the vesicular stomatitis virus (VSV) encephalitis model. VSV is a rhabdovirus that causes severe and rapid encephalitis accompanied by microgliosis in mice after intranasal infection[10]. This virus has been shown to infect neuroepithelial cells, and is widely used as a model of acute neurotropic CNS infection[11,12]. To gain further insights on inhibitory effects of ganciclovir on microglial proliferation, in vitro experiments with murine microglial cultures were performed
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