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The antiviral drug ganciclovir does not inhibit microglial proliferation and activation.

Skripuletz T, Salinas Tejedor L, Prajeeth CK, Hansmann F, Chhatbar C, Kucman V, Zhang N, Raddatz BB, Detje CN, Sühs KW, Pul R, Gudi V, Kalinke U, Baumgärtner W, Stangel M - Sci Rep (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.

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.

No MeSH data available.


Related in: MedlinePlus

The effects of ganciclovir were investigated in Theiler’s murine encephalomyelitis virus (TMEV) infected C57BL/6 mice and in corresponding non-infected controls.Virus infection (A,B) and T cell infiltration (C,D) were confirmed by immunohistochemical stainings in the hippocampus. Total microglia numbers were analyzed by Iba1 staining, while proliferating microglia were visualized by double staining for Iba1/Ki67 (E,F). No effects of ganciclovir on virus infected neurons and T cell and microglial numbers could be observed between TMEV groups. Each bar represents the mean ± SEM, n = 6 per time point and group.
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f1: The effects of ganciclovir were investigated in Theiler’s murine encephalomyelitis virus (TMEV) infected C57BL/6 mice and in corresponding non-infected controls.Virus infection (A,B) and T cell infiltration (C,D) were confirmed by immunohistochemical stainings in the hippocampus. Total microglia numbers were analyzed by Iba1 staining, while proliferating microglia were visualized by double staining for Iba1/Ki67 (E,F). No effects of ganciclovir on virus infected neurons and T cell and microglial numbers could be observed between TMEV groups. Each bar represents the mean ± SEM, n = 6 per time point and group.

Mentions: TME virus (TMEV) induced neuroinflammation is predominantly found in the hippocampus within the first weeks of infection131415. In our experiments, TMEV infection of mice was confirmed by immunohistochemical stainings of virus particles (Fig. 1A,B) and of T cell infiltration (Fig. 1C,D) in the hippocampus and total brain (data not shown). In this model, virus clearance is fast and only few infected cells could be detected after two weeks of infection (Fig. 1A,B). We found that TMEV infection is accompanied by prominent microglial proliferation and activation (Fig. 1E,F) as also previously observed by others16. As compared to non-infected controls, significantly higher numbers of proliferating microglia (Iba1+/Ki67+) and total numbers of microglia (Iba1+) were found in the hippocampus. Proliferating microglia was detected in high numbers after one week of infection and decreased in numbers at week two.


The antiviral drug ganciclovir does not inhibit microglial proliferation and activation.

Skripuletz T, Salinas Tejedor L, Prajeeth CK, Hansmann F, Chhatbar C, Kucman V, Zhang N, Raddatz BB, Detje CN, Sühs KW, Pul R, Gudi V, Kalinke U, Baumgärtner W, Stangel M - Sci Rep (2015)

The effects of ganciclovir were investigated in Theiler’s murine encephalomyelitis virus (TMEV) infected C57BL/6 mice and in corresponding non-infected controls.Virus infection (A,B) and T cell infiltration (C,D) were confirmed by immunohistochemical stainings in the hippocampus. Total microglia numbers were analyzed by Iba1 staining, while proliferating microglia were visualized by double staining for Iba1/Ki67 (E,F). No effects of ganciclovir on virus infected neurons and T cell and microglial numbers could be observed between TMEV groups. Each bar represents the mean ± SEM, n = 6 per time point and group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4597339&req=5

f1: The effects of ganciclovir were investigated in Theiler’s murine encephalomyelitis virus (TMEV) infected C57BL/6 mice and in corresponding non-infected controls.Virus infection (A,B) and T cell infiltration (C,D) were confirmed by immunohistochemical stainings in the hippocampus. Total microglia numbers were analyzed by Iba1 staining, while proliferating microglia were visualized by double staining for Iba1/Ki67 (E,F). No effects of ganciclovir on virus infected neurons and T cell and microglial numbers could be observed between TMEV groups. Each bar represents the mean ± SEM, n = 6 per time point and group.
Mentions: TME virus (TMEV) induced neuroinflammation is predominantly found in the hippocampus within the first weeks of infection131415. In our experiments, TMEV infection of mice was confirmed by immunohistochemical stainings of virus particles (Fig. 1A,B) and of T cell infiltration (Fig. 1C,D) in the hippocampus and total brain (data not shown). In this model, virus clearance is fast and only few infected cells could be detected after two weeks of infection (Fig. 1A,B). We found that TMEV infection is accompanied by prominent microglial proliferation and activation (Fig. 1E,F) as also previously observed by others16. As compared to non-infected controls, significantly higher numbers of proliferating microglia (Iba1+/Ki67+) and total numbers of microglia (Iba1+) were found in the hippocampus. Proliferating microglia was detected in high numbers after one week of infection and decreased in numbers at week two.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.

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.

No MeSH data available.


Related in: MedlinePlus