The type 2 diabetes drug liraglutide reduces chronic inflammation induced by irradiation in the mouse brain

Journal article


Parthsarathy, Vadivel and Holscher, Christian 2013. The type 2 diabetes drug liraglutide reduces chronic inflammation induced by irradiation in the mouse brain. European Journal of Pharmacology. 700 (1-3), pp. 42-50. https://doi.org/10.1016/j.ejphar.2012.12.012
AuthorsParthsarathy, Vadivel and Holscher, Christian
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.

Keywordsneurodegenerative diseases; Alzheimer's disease; Parkinson's disease; infection; incretins; liraglutide
Year2013
JournalEuropean Journal of Pharmacology
Journal citation700 (1-3), pp. 42-50
PublisherElsevier
ISSN0014-2999
Digital Object Identifier (DOI)https://doi.org/10.1016/j.ejphar.2012.12.012
Web address (URL)http://hdl.handle.net/10545/622910
hdl:10545/622910
http://europepmc.org/article/med/23276669
Output statusPublished
Publication dates28 Dec 2012
Publication process dates
Deposited16 Aug 2018
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