Hülskötter, K., Lühder, F., Flügel, A., Herder, V. and Baumgärtner, W. (2021) Tamoxifen application is associated with transiently increased loss of hippocampal neurons following virus infection. International Journal of Molecular Sciences, 22(16), 8486. (doi: 10.3390/ijms22168486) (PMID:34445189) (PMCID:PMC8395206)
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Abstract
Tamoxifen is frequently used in murine knockout systems with CreER/LoxP. Besides possible neuroprotective effects, tamoxifen is described as having a negative impact on adult neurogenesis. The present study investigated the effect of a high-dose tamoxifen application on Theiler’s murine encephalomyelitis virus (TMEV)-induced hippocampal damage. Two weeks after TMEV infection, 42% of the untreated TMEV-infected mice were affected by marked inflammation with neuronal loss, whereas 58% exhibited minor inflammation without neuronal loss. Irrespective of the presence of neuronal loss, untreated mice lacked TMEV antigen expression within the hippocampus at 14 days post-infection (dpi). Interestingly, tamoxifen application 0, 2 and 4, or 5, 7 and 9 dpi decelerated virus elimination and markedly increased neuronal loss to 94%, associated with increased reactive astrogliosis at 14 dpi. T cell infiltration, microgliosis and expression of water channels were similar within the inflammatory lesions, regardless of tamoxifen application. Applied at 0, 2 and 4 dpi, tamoxifen had a negative impact on the number of doublecortin (DCX)-positive cells within the dentate gyrus (DG) at 14 dpi, without a long-lasting effect on neuronal loss at 147 dpi. Thus, tamoxifen application during a TMEV infection is associated with transiently increased neuronal loss in the hippocampus, increased reactive astrogliosis and decreased neurogenesis in the DG.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Herder, Dr Vanessa |
Creator Roles: | |
Authors: | Hülskötter, K., Lühder, F., Flügel, A., Herder, V., and Baumgärtner, W. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
Journal Name: | International Journal of Molecular Sciences |
Publisher: | MDPI |
ISSN: | 1661-6596 |
ISSN (Online): | 1422-0067 |
Published Online: | 06 August 2021 |
Copyright Holders: | Copyright © 2021 The Authors |
First Published: | First published in International Journal of Molecular Sciences 22(16): 8486 |
Publisher Policy: | Reproduced under a Creative Commons License |
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