Tamoxifen application is associated with transiently increased loss of hippocampal neurons following virus infection

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)

[img] Text
266262.pdf - Published Version
Available under License Creative Commons Attribution.



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
Glasgow Author(s) Enlighten ID:Herder, Dr Vanessa
Creator Roles:
Herder, V.Conceptualization, Investigation, Writing – review and editing, Project administration
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
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

University Staff: Request a correction | Enlighten Editors: Update this record