Tamoxifen gavage is a commonly used method to induce genetic modifications in cre-loxP systems. As a
selective estrogen receptor modulator (
SERM), the compound is known to have immunomodulatory and neuroprotective properties in non-infectious central nervous system (CNS) disorders. It can even cause complete prevention of lesion development as seen in experimental
autoimmune encephalitis (EAE). The effect on infectious
brain disorders is scarcely investigated. In this study, susceptible SJL mice were infected intracerebrally with Theiler's murine encephalomyelitis virus (TMEV) and treated three times with a
tamoxifen-in-oil-gavage (TOG), resembling an application scheme for genetically modified mice, starting at 0, 18, or 38 days post
infection (dpi). All mice developed 'TMEV-induced
demyelinating disease' (TMEV-IDD) resulting in
inflammation, axonal loss, and
demyelination of the spinal cord. TOG had a positive effect on the numbers of oligodendrocytes and oligodendrocyte progenitor cells, irrespective of the time point of application, whereas late application (starting 38 dpi) was associated with increased
demyelination of the spinal cord white matter 85 dpi. Furthermore, TOG had differential effects on the CD4+ and CD8+ T cell infiltration into the CNS, especially a long lasting increase of CD8+ cells was detected in the inflamed spinal cord, depending of the time point of TOG application. Number of TMEV-positive cells,
astrogliosis, astrocyte phenotype, apoptosis, clinical score, and motor function were not measurably affected. These data indicate that
tamoxifen gavage has a double-edged effect on TMEV-IDD with the promotion of oligodendrocyte differentiation and proliferation, but also increased
demyelination, depending on the time point of application. The data of this study suggest that
tamoxifen has also partially protective functions in infectious
CNS disease. These effects should be considered in experimental studies using the cre-loxP system, especially in models investigating neuropathologies.