Metabolic Alterations Amalgamated with Huntington’s Disease

Insights into Human Neurodegeneration: Lessons Learnt from Drosophila ◽

10.1007/978-981-13-2218-1_6 ◽

2019 ◽

pp. 163-183

Author(s):

Priya Lakra ◽

Namita Agrawal

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Metabolic Alterations

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Metabolic Alterations in an Animal Model of Huntington’s Disease Using the 14C-Deoxyglucose Method

Current Topics in Extrapyramidal Disorders ◽

10.1007/978-3-7091-8582-7_11 ◽

1980 ◽

pp. 103-109

Author(s):

H. Kimura ◽

Edith G. McGeer ◽

P. L. McGeer

Keyword(s):

Animal Model ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Metabolic Alterations ◽

Deoxyglucose Method

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Impaired Brain Energy Metabolism in the BACHD Mouse Model of Huntington's Disease: Critical Role of Astrocyte–Neuron Interactions

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2014.110 ◽

2014 ◽

Vol 34 (9) ◽

pp. 1500-1510 ◽

Cited By ~ 25

Author(s):

Lydie Boussicault ◽

Anne-Sophie Hérard ◽

Noel Calingasan ◽

Fanny Petit ◽

Carole Malgorn ◽

...

Keyword(s):

Energy Metabolism ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Molecular Mechanisms ◽

Critical Role ◽

Cag Repeat ◽

Metabolic Alterations ◽

Culture Models ◽

Repeat Expansions

Huntington's disease (HD) is caused by cytosine-adenine-guanine (CAG) repeat expansions in the huntingtin (Htt) gene. Although early energy metabolic alterations in HD are likely to contribute to later neurodegenerative processes, the cellular and molecular mechanisms responsible for these metabolic alterations are not well characterized. Using the BACHD mice that express the full-length mutant huntingtin (mHtt) protein with 97 glutamine repeats, we first demonstrated localized in vivo changes in brain glucose use reminiscent of what is observed in premanifest HD carriers. Using biochemical, molecular, and functional analyses on different primary cell culture models from BACHD mice, we observed that mHtt does not directly affect metabolic activity in a cell autonomous manner. However, coculture of neurons with astrocytes from wild-type or BACHD mice identified mutant astrocytes as a source of adverse non-cell autonomous effects on neuron energy metabolism possibly by increasing oxidative stress. These results suggest that astrocyte-to-neuron signaling is involved in early energy metabolic alterations in HD.

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