title: The type 2 diabetes drug liraglutide reduces chronic inflammation induced by irradiation in the mouse brain.
abstract: Chronic inflammation in the brain is found in a range of neurodegenerative diseases such as Parkinson's or Alzheimer's disease. We have recently shown that analogues of the glucagon-like polypeptide 1 (GLP-1) such as liraglutide have potent neuroprotective properties in a mouse model of Alzheimer's disease. We also found a reduction of activated microglia in the brain. This finding suggests that GLP-1 analogues such as liraglutide have anti-inflammatory properties. To further characterise this property, we tested the effects of liraglutide on the chronic inflammation response induced by exposure of the brain to 6 Gy (X-ray). Animals were injected i.p. with 25 nmol/kg once daily for 30 days. Brains were analysed for cytokine levels, activated microglia and astrocyte levels, and nitrite levels as a measure for nitric oxide production and protein expression of iNOS. Exposure of the brain to 6 Gy induced a pronounced chronic inflammation response in the brain. The activated microglia load in the cortex and dentate gyrus region of hippocampus (P<0.001), and the activated astrocyte load in the cortex (P<0.01) was reduced by liraglutide. Furthermore, the pro-inflammatory cytokine levels of IL-6 (P<0.01), IL-12p70 (P<0.01), IL-1β (P<0.05), and total nitrite concentration were reduced in the brains of animals treated with liraglutide. The results demonstrate that liraglutide is effective in reducing a number of parameters linked to the chronic inflammation response. Liraglutide or similar GLP-1 analogues may be a suitable treatment for reducing the chronic inflammatory response in the brain found in several neurodegenerative conditions.
authors.affiliation: School of Biomedical Sciences, Ulster University, Cromore Road, BT52 1SA Coleraine, Northern Ireland.
authors.forename: Vadivel
authors.initials: V
authors.lastname: Parthsarathy
authors.forename: Christian
authors.initials: C
authors.lastname: Hölscher
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D001835:Body Weight / Q000187:drug effects / Q000528:radiation effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D016207:Cytokines / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004435:Eating / Q000187:drug effects / Q000528:radiation effects; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000069450:Liraglutide; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D009573:Nitrites; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D052247:Nitric Oxide Synthase Type II