Ghrelin‐mediated improvements in the metabolic phenotype in the R6/2 mouse model of Huntington's disease

• DOI: 10.1111/jne.12699
• Publication Date: 2019-02-18T14:58:56Z
• Authors: Olga Rudenko; Cecilie Springer; Louisa J. Skov; Andreas N. Madsen; Lis Hasholt; Anne Nørremølle; Birgitte Holst
• Keywords: 0303 health sciences; Huntington's disease; Mice, Transgenic; Motor Activity; Ghrelin; Circadian Rhythm; Disease Models, Animal; Eating; 03 medical and health sciences; Huntington Disease; Phenotype; ghrelin; Body Composition; R6/2 mouse model; Animals; Female; Energy Metabolism; metabolism

Abstract Huntington's disease ( HD ) is a heritable neurodegenerative disorder, characterised by metabolic disturbances, along with cognitive and psychiatric impairments. Targeting dysfunction via the maintenance of body weight fat mass restoration peripheral energy metabolism can improve progression neurological symptoms. In this respect, we focused on therapeutic potential orexigenic peptide hormone ghrelin, which plays an important role in promoting positive balance. present study, found significant disruption circadian regulation R6/2 mouse model late stage disease. Daily rhythms activity, expenditure, respiratory exchange ratio feeding were strongly attenuated mice. During rest phase, mice had higher total elevated expenditure excessive water consumption compared to control We also that, disease, ghrelin axis deficiency as result low circulating levels, addition down‐regulation receptor several key signalling molecules hypothalamus, well reduced responsiveness exogenous ghrelin. demonstrated pre‐symptomatic mice, preserved. Chronic treatment efficiently increased lean decreased utilisation early addition, was effective normalisation drinking behaviour activity these Ghrelin could provide novel possibility for delaying progression; however, expression limit its