Is DPP4/GLP-1 pathway a possible target for remyelination? – A first cerebellum-focused approach using the cuprizone mouse model
ECTRIMS Online Library. Palavra F. 10/25/17; 199480; EP1460
Filipe Palavra
Filipe Palavra

Abstract: EP1460

Type: ePoster

Abstract Category: Pathology and pathogenesis of MS - 13 Experimental models

Introduction: Cuprizone (CPZ) is a copper chelator that produces a reversible oligodendrocytopathy in animals, similar to human multiple sclerosis (MS). This model is attractive to study remyelination, but some of its fundamental properties are not yet fully characterized.
Aims: To deepen the knowledge about the biochemical profile associated with CPZ-induced demyelination and subsequent remyelination in the cerebellum, focusing on gliosis, inflammation markers and on the dipeptidyl-peptidase 4 (DPP4)/glucagon-like peptide-1 (GLP-1) pathway.
Material and methods: Two groups of male C57BL/6 mice (n=10 each) were fed an oral solution of CPZ (0.2%) for 5 weeks (W5); half of the animals were subsequently kept under treatment with the vehicle (water) for another 2 weeks (W7). A vehicle-treated group was used as a control. After 5 and 7 weeks, the animals were subjected to gene expression and/or protein analysis studies of GFAP, myelin proteolipid protein (PLP), TNF-α, IL-1β, DPP4, GLP-1 and GLP-1R in the cerebellum, using techniques of RT-PCR, western blot and immunohistochemistry.
Results: Myelin PLP expression decreased in the cerebellum of CPZ-treated animals (W5), and these changes reverted at 7 weeks. GFAP levels varied in the opposite direction. The model also corroborated the existence of an underlying inflammatory process, revealed by the elevated expression of TNF-α and IL-1β in W5, normalizing in W7. Finally, the lack of changes in DPP4 and GLP-1 levels was accompanied by a reduction in GLP-1R levels in the cerebellum of W5 animals, as revealed by western blot.
Conclusion: The observed changes validate the use of W5 and W7 temporal moments for the study of demyelination and early remyelination in the cerebellum of these animals. The expression profile of DPP4, GLP-1 and GLP-1R maintains intact the possibility of using this pathway as a possible therapeutic target in MS.
Disclosure: Portuguese Foundation for Science and Technology (Strategic Projects Pest-C/SAU/UI3282/2013 and UID/NEU/04539/2013), COMPETE (POCI-01-0145-FEDER-007440) and Biogen.

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