title: The antiviral drug ganciclovir does not inhibit microglial proliferation and activation.
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.
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Skripuletz
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.|Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Salinas Tejedor
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Chittappen K
authors.initials: CK
authors.lastname: Prajeeth
authors.affiliation: Center for Systems Neuroscience, Hannover, Germany.|Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Hansmann
authors.affiliation: Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
authors.forename: Chintan
authors.initials: C
authors.lastname: Chhatbar
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Valeria
authors.initials: V
authors.lastname: Kucman
authors.affiliation: Center for Systems Neuroscience, Hannover, Germany.|Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Center for Systems Neuroscience, Hannover, Germany.|Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Raddatz
authors.affiliation: Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
authors.forename: Claudia N
authors.initials: CN
authors.lastname: Detje
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Kurt-Wolfram
authors.initials: KW
authors.lastname: Sühs
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Refik
authors.initials: R
authors.lastname: Pul
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Gudi
authors.affiliation: Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kalinke
authors.affiliation: Center for Systems Neuroscience, Hannover, Germany.|Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumgärtner
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.|Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Stangel
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000998:Antiviral Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000821:virology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000517:prevention & control; D004195:Disease Models, Animal; D004679:Encephalomyelitis / Q000517:prevention & control / Q000821:virology; D015774:Ganciclovir / Q000494:pharmacology*; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D017945:Theilovirus / Q000502:physiology; D054243:Vesicular Stomatitis / Q000517:prevention & control / Q000821:virology; D018116:Vesiculovirus / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D003471:Cuprizone; D015774:Ganciclovir