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- W2891676595 abstract "Background Huntington’s disease (HD) is characterized by cortico-striatal neuronal loss, energy dysmetabolism and type 2 diabetes (T2D) features. Thus, an efficient anti-T2D drug like liraglutide may protect against HD. Albeit the HD-related cachexia and liraglutide’s anorectic features, its peripheral (co-) administration with the orexigenic ghrelin may protect against brain/cognitive deficits in HD. Aims We analyzed the effect of subcutaneous (sc) (co-)injection of liraglutide plus ghrelin in brain mitochondrial metabolism markers and motor function in HD. Methods Brain cortices from 11 weeks R6/2 and WT mice sc-treated with liraglutide and/or ghrelin (2 weeks) were used to measure mitochondria-related metabolic markers and respiratory chain complexes’ activities. Motor/exploratory activity was given by paw clasping and open-field test. Results Liraglutide alone or plus ghrelin rescued peripheral T2D features in R6/2 mice. Preliminary data on citrate synthase and mitochondrial respiratory chain complex I activities showed a slight inhibition in brains from R6/2 mice, which also had lower ADP levels and higher ATP/ADP. All parameters were partially normalized by sc liraglutide. Liraglutide plus ghrelin lowered AMP levels in R6/2 mice, increasing their brain energy status. This suggests that liraglutide per se or plus ghrelin may stimulate brain cortical glucose (mitochondrial) metabolism in R6/2 mice. Paw clasping was increased in R6/2 mice but did not change after liraglutide alone or plus ghrelin. No changes occurred in locomotor and exploratory activities in open-field test. Conclusions Liraglutide per se or plus ghrelin appear to recover brain cortical glucose dysmetabolism in R6/2 mice, encouraging further studies on brain energy metabolism in HD. Supported by EU funds from FEDER – Programa Operacional Factores de Competitividade, COMPETE 2020; by a Seed Fund from European Huntington’s Disease Network (EHDN); by Swedish Research Council; by Neuro Sweden; by Kocks Foundation; by Portuguese funds from FCT (PTDC/NEU-NMC/0412/2014; PTDC/SAU-TOX/117481/2010); and by European Social Fund (SFRH/BPD/84473/2012 to A.I. Duarte)." @default.
- W2891676595 created "2018-09-27" @default.
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- W2891676595 date "2018-09-01" @default.
- W2891676595 modified "2023-09-22" @default.
- W2891676595 title "I11 Effects of dual administration of liraglutide and ghrelin on brain mitochondrial metabolism in the r6/2 mouse" @default.
- W2891676595 doi "https://doi.org/10.1136/jnnp-2018-ehdn.247" @default.
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