RESUMO
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.
Assuntos
Proliferação de Células/efeitos dos fármacos , Ganciclovir/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Microglia/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Antivirais/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/virologia , Células Cultivadas , Cuprizona , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/prevenção & controle , Modelos Animais de Doenças , Encefalomielite/prevenção & controle , Encefalomielite/virologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Ativação de Macrófagos/imunologia , Camundongos Endogâmicos C57BL , Microglia/imunologia , Microglia/patologia , Theilovirus/fisiologia , Estomatite Vesicular/prevenção & controle , Estomatite Vesicular/virologia , Vesiculovirus/fisiologiaRESUMO
Oligodendrocytes are the myelinating cells of the central nervous system. Since many studies of demyelinating diseases focus their research on this cell type, there is growing interest for obtaining reliable markers that can specifically recognize oligodendroglia. Established markers are the myelin-associated neurite outgrowth inhibitor (NogoA), the transcription factor Olig2, and the antibody CC-1, the latter being directed against the protein adenomatous polyposis coli (APC). Unfortunately, it has been discussed whether APC and Olig2 could recognize astrocytes under pathological conditions as well. Hence, we performed immunohistochemical studies using the oligodendroglial markers NogoA, APC, and Olig2 in a murine model of cuprizone induced demyelination. We have found that APC co-localizes with NogoA and does not co-localize with the astrocytic marker GFAP. Olig2 shows co-localization with APC but there is also a small population of Olig2/GFAP double positive cells. Some Olig2/GFAP double positive cells are found in the corpus callosum in a narrow time window in which oligodendrocyte precursor cells proliferate in this model. In other brain regions including the cerebral cortex and hippocampus and in all regions in untreated control mice double positive Olig2/GFAP cells do not occur. In conclusion, our results underline that APC and NogoA are reliable markers for detection of mature oligodendrocytes. Olig2 is a suitable marker to stain cells of oligodendroglial origin but could be combined with GFAP to exclude the GFAP positive population of cells from the quantification of oligodendroglia.