Analysis of neurogenesis during experimental autoimmune encephalomyelitis reveals pitfalls of bioluminescence imaging

  • Bioluminescence imaging is a sensitive approach for longitudinal neuroimaging. Transgenic mice expressing luciferase under the promoter of doublecortin (DCX-luc), a specific marker of neuronal progenitor cells (NPC), allow monitoring of neurogenesis in living mice. Since the extent and time course of neurogenesis during autoimmune brain inflammation are controversial, we investigated neurogenesis in MOG-peptide induced experimental allergic encephalomyelitis (EAE) using DCX-luc reporter mice. We observed a marked, 2- to 4-fold increase of the bioluminescence signal intensity 10 days after EAE induction and a gradual decline 1–2 weeks thereafter. In contrast, immunostaining for DCX revealed no differences between EAE and control mice 2 and 4 weeks after immunization in zones of adult murine neurogenesis such as the dentate gyrus. \(\textit {Ex vivo}\) bioluminescence imaging showed similar luciferase expression in brain homogenates of EAE and control animals. Apart from complete immunization including MOG-peptide also incomplete immunization with complete Freund´s adjuvant and pertussis toxin resulted in a rapid increase of the \(\textit {in vivo}\) bioluminescence signal. Blood-brain barrier (BBB) leakage was demonstrated 10 days after both complete and incomplete immunization and might explain the increased bioluminescence signal \(\textit {in vivo}\). We conclude, that acute autoimmune inflammation in EAE does not alter neurogenesis, at least at the stage of DCX-expressing NPC. Effects of immunization on the BBB integrity must be considered when luciferase is used as a reporter within the CNS during the active stage of EAE. Models with stable CNS-restricted luciferase expression could serve as technically convenient way to evaluate BBB integrity in a longitudinal manner.

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Metadaten
Author:Ilya AyzenbergORCiDGND, Sibylle Dorothea SchlevogtGND, Judith MetzdorfGND, Sarah StahlkeGND, Xiomara PedreitturiaGND, Anika HunfeldGND, Sebastien Couillard-DespresORCiDGND, Ingo Wolfram KleiterGND
URN:urn:nbn:de:hbz:294-73390
DOI:https://doi.org/10.1371/journal.pone.0118550
Parent Title (English):PLoS ONE
Publisher:Public Library of Science
Place of publication:San Francisco
Document Type:Article
Language:English
Date of Publication (online):2020/07/15
Date of first Publication:2015/03/17
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Volume:10
Issue:3, Artikel e0118550
First Page:e0118550-1
Last Page:e0118550-10
Institutes/Facilities:St. Josef-Hospital Bochum, Neurologische Klinik
open_access (DINI-Set):open_access
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International