In vivo imaging of brain damage by use of luciferase-enabled light emission and supersensitve cameras

• Unité de recherche: COST
• Numéro de projet: C07.0132
• Titre du projet anglais: In vivo imaging of brain damage by use of luciferase-enabled light emission and supersensitve cameras

Mots-clé (Anglais)

Luciferase; Oligodendrocyte; Demyelination; EAE; Cuprizone

Programme de recherche (Anglais)

COST-Action BM0603 - Inflammation in brain disease

Description succincte (Anglais)

See abstract

Autres indications (Anglais)

Full name of research-institution/enterprise: Universität Zürich Medizinische Fakultät Institut für Experimentelle Immunologie

Partenaires et organisations internationales (Anglais)

AT, CH, DE, DK, EL, ES, FR, IE, IL, IT, NL, NO, PL, PT, RS, SE, UK

Résumé des résultats (Abstract) (Anglais)

In order to follow the in vivo dynamics of demyelination and remyelination, we have generated a novel mouse model (oLucR) which expresses luciferase specifically in mature oligodendrocytes (ODCs). We achieved this by crossing mice expressing the Cre recombinase under control of the myelin oligodendrocyte glycoprotein promoter (MOGi-Cre mice) with reporter mice expressing a Cre-inducible luciferase gene under an ubiquitous b-actin promoter (Lyons et al. 2003). The mice are shaved, anesthetized and quantitatively measured in an ultrasensitive IVIS machine (Xenogen) after i.p. injection of luciferin. We followed bioluminescence changes in different experimental demyelinating models, namely Cuprizone-fed mice, DT-treated oDTR animals (ODCs expressing the Diphtheria Toxin Receptor, Buch et al 2005) and MOG-immunized mice developing experimental autoimmune encephalomyelisits (EAE). Since only mature ODCs express the luciferase gene, our aim was to investigate the dynamics of ODC death/demyelination and subsequent remyelination through light emission recordings. Both after DT- and cuprizone- induced demyelination we could detect in vivo remyelination through an increase in bioluminescence approximately 40 days after the initial administration. The timing of this emission peak coincide with the final stage of differentiation of the ODC progenitors (OPCs). Also, in all experiments and especially following EAE induction, we could detect a strong and sharp luciferase emission increase around the onset of ODC death. These unexpected 'early' emission peaks in both disease models represent most likely a combination between increased blood brain barrier (BBB) permeability and increased expression of the b-actin-driven luciferase gene in metabolically active ODCs under stress conditions. In every experiment, in vitro bioluminescence measured via luminometer/ ex vivo bioluminescence measured in luciferin-bathed brain slices correlate with the in vivo data showing that this phenomenon is an intrinsic feature of the damaged ODC population and not a mere in vivo artifact. In parallel to the oLucR mice, we have been testing a novel mouse model expressing luciferase specifically in CD4 T cells (CD4-LucR mice). In these animals, CD4 T cell invasion in the spinal cord during the course of MOG-induced EAE could be quantified in vivo, thus providing a new method to score EAE progression.

Références bases de données (Anglais)

Swiss Database: COST-DB of the State Secretariat for Education and Research Hallwylstrasse 4 CH-3003 Berne, Switzerland Tel. [phone] Swiss Project-Number: C07.0132