Glucagon-like peptide-1 analog, Liraglutide, delays onset of experimental autoimmune encephalitis in Lewis rats
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- Glucagon-Like Peptide-1 Analog, Liraglutide, Delays Onset of Experimental Autoimmune Encephalitis in Lewis Rats
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Brian William Della Valle, Gitte S. Brix, Birgitte Brock, Michael Gejl, Anne M. Landau, Arne Moller, Jorgen Rungby, Agnete Larsen
Methods: EAE was induced in 30 female Lewis rats that subsequently received twice-daily liraglutide (200 μg/kg s.c.) or saline. Healthy controls were included (saline, n = 6, liraglutide, n = 7). Clinical score and weight were assessed daily by blinded observers. Animals were killed at peak disease severity (day 11) or if exceeding humane endpoint (clinical score ≥4). Protein levels of manganese superoxide dismutase (MnSOD), amyloid precursor protein (APP), and glial fibrillary acidic protein (GFAP) were determined.
Results: Liraglutide treatment delayed disease onset (group clinical score significantly >0) by 2 days and markedly reduced disease severity (median clinical score 2 vs. 5; p = 0.0003). Fourteen of 15 (93%) of vehicle-treated rats reached the humane endpoint (clinical score ≥4) by day 11 compared to 5 of 15 (33%) of liraglutide-treated rats (p = 0.0004). Liraglutide substantially increased the mitochondrial antioxidant MnSOD (p < 0.01) and reduced the neurodegenerative marker APP (p = 0.036) in the brain. GFAP levels were not significantly changed with drug treatment (p = 0.09).
Conclusion: We demonstrate, for the first time, that liraglutide treatment delays onset of EAE in Lewis rats and is associated with improved protective capacity against oxidative stress. These data suggest GLP-1 receptor agonists should be investigated further as a potential therapy for MS
|Tidsskrift||Frontiers in Pharmacology|
|Status||Udgivet - 18 nov. 2016|
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