Journal
MOLECULAR NEUROBIOLOGY
Volume 49, Issue 3, Pages 1126-1142Publisher
HUMANA PRESS INC
DOI: 10.1007/s12035-013-8585-5
Keywords
Huntington's disease; IGF-1; YAC128 mice; Huntingtin phosphorylation; Energy metabolism; Signaling pathways; Animal behavior
Categories
Funding
- Fundacao para a Ciencia e a Tecnologia (FCT), Portugal [PTDC/SAU-FCF/66421/2006, PTDC/SAU-FCF/108056/2008]
- COMPETE-Programa Operacional Factores de Competitividade
- QREN
- European Union (FEDER-Fundo Europeu de Desenvolvimento Regional)
- FCT [SFRH/BD/51192/2010, SFRH/BD/41285/2007, SFRH/BPD/26872/2006]
- [PEst-C/SAU/LA0001/2013-2014]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/51192/2010, SFRH/BD/41285/2007, PTDC/SAU-FCF/66421/2006, SFRH/BPD/26872/2006] Funding Source: FCT
Ask authors/readers for more resources
Huntington's disease (HD) is an autosomal dominant disease caused by an expansion of CAG repeats in the gene encoding for huntingtin. Brain metabolic dysfunction and altered Akt signaling pathways have been associated with disease progression. Nevertheless, conflicting results persist regarding the role of insulin-like growth factor-1 (IGF-1)/Akt pathway in HD. While high plasma levels of IGF-1 correlated with cognitive decline in HD patients, other data showed protective effects of IGF-1 in HD striatal neurons and R6/2 mice. Thus, in the present study, we investigated motor phenotype, peripheral and central metabolic profile, and striatal and cortical signaling pathways in YAC128 mice subjected to intranasal administration of recombinant human IGF-1 (rhIGF-1) for 2 weeks, in order to promote IGF-1 delivery to the brain. We show that IGF-1 supplementation enhances IGF-1 cortical levels and improves motor activity and both peripheral and central metabolic abnormalities in YAC128 mice. Moreover, decreased Akt activation in HD mice brain was ameliorated following IGF-1 administration. Upregulation of Akt following rhIGF-1 treatment occurred concomitantly with increased phosphorylation of mutant huntingtin on Ser421. These data suggest that intranasal administration of rhIGF-1 ameliorates HD-associated glucose metabolic brain abnormalities and mice phenotype.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available