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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: Ganciclovir is effective in the treatment of human infections with viruses of the Herpesviridae family.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 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 on the proliferation and viability of microglia in vitro using primary microglia cultures.Different doses of ganciclovir (0.05–1 mM) did not change microglial proliferation as shown by analysis of BrdU+ cells (A,B). The percentage of annexin V+ (early apoptotic), annexin V+ PI+ (late apoptotic), and PI+ (necrotic) cells was not changed by ganciclovir indicating that ganciclovir did not influence survival of cells. Each data represents the mean ± SEM, n = 4.
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f4: The effects of ganciclovir were investigated on the proliferation and viability of microglia in vitro using primary microglia cultures.Different doses of ganciclovir (0.05–1 mM) did not change microglial proliferation as shown by analysis of BrdU+ cells (A,B). The percentage of annexin V+ (early apoptotic), annexin V+ PI+ (late apoptotic), and PI+ (necrotic) cells was not changed by ganciclovir indicating that ganciclovir did not influence survival of cells. Each data represents the mean ± SEM, n = 4.

Mentions: To determine whether ganciclovir might induce any cytotoxic effects on resting and activated microglia, additional in vitro experiments were performed. First, the effects of ganciclovir on microglial proliferation were studied. Our results show that approximately 35% of microglia harvested from neonatal brain mixed glial cultures exhibited proliferation after re-plating, as demonstrated by incorporation of BrdU into these cells. Treatment with low doses of ganciclovir (0.05–0.1 mM) for 48 h did not have any impact on the proliferation of microglia (Fig. 4). At higher doses of ganciclovir (0.2–1 mM) a small decrease in the number of BrdU+ cells occurred, but this reduction did not yield a statistical significance (Fig. 4A,B).


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 on the proliferation and viability of microglia in vitro using primary microglia cultures.Different doses of ganciclovir (0.05–1 mM) did not change microglial proliferation as shown by analysis of BrdU+ cells (A,B). The percentage of annexin V+ (early apoptotic), annexin V+ PI+ (late apoptotic), and PI+ (necrotic) cells was not changed by ganciclovir indicating that ganciclovir did not influence survival of cells. Each data represents the mean ± SEM, n = 4.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: The effects of ganciclovir were investigated on the proliferation and viability of microglia in vitro using primary microglia cultures.Different doses of ganciclovir (0.05–1 mM) did not change microglial proliferation as shown by analysis of BrdU+ cells (A,B). The percentage of annexin V+ (early apoptotic), annexin V+ PI+ (late apoptotic), and PI+ (necrotic) cells was not changed by ganciclovir indicating that ganciclovir did not influence survival of cells. Each data represents the mean ± SEM, n = 4.
Mentions: To determine whether ganciclovir might induce any cytotoxic effects on resting and activated microglia, additional in vitro experiments were performed. First, the effects of ganciclovir on microglial proliferation were studied. Our results show that approximately 35% of microglia harvested from neonatal brain mixed glial cultures exhibited proliferation after re-plating, as demonstrated by incorporation of BrdU into these cells. Treatment with low doses of ganciclovir (0.05–0.1 mM) for 48 h did not have any impact on the proliferation of microglia (Fig. 4). At higher doses of ganciclovir (0.2–1 mM) a small decrease in the number of BrdU+ cells occurred, but this reduction did not yield a statistical significance (Fig. 4A,B).

Bottom Line: Ganciclovir is effective in the treatment of human infections with viruses of the Herpesviridae family.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 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