ArticleThe Journal of biological chemistry2012
Early alterations of brain cellular energy homeostasis in Huntington disease models.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 112 citations in OpenAlex.
- Trial
- A study of molecular changes relating to energy metabolism and cellular stress in people with Huntington's disease: looking for biomarkers.Journal of bioenergetics and biomembranes · 2013Trial
- Understanding Energy Expenditure: An Approach to Improving Activities of Daily Living in Huntington's Disease.Journal of clinical medicine · 2026Article
- Mitochondrial dysfunction in cellular senescence: a bridge to neurodegenerative disease.npj aging · 2025Review
- Stage-Dependent Inhibitory Connectivity in Striatal-Motor Circuit in Huntington's Disease.Annals of clinical and translational neurology · 2025Article
- From Pathogenesis to Therapeutics: A Review of 150 Years of Huntington's Disease Research.International journal of molecular sciences · 2023Review
- Interactions of amyloidogenic proteins with mitochondrial protein import machinery in aging-related neurodegenerative diseases.Frontiers in physiology · 2023Review
- Longitudinal multimodal MRI characterization of a knock-in mouse model of Huntington's disease reveals early gray and white matter alterations.Human molecular genetics · 2022Article
- Article
- Article
- Multiplatform metabolomic analysis of the R6/2 mouse model of Huntington's disease.FEBS open bio · 2021Article
- Accelerated expansion of pathogenic mitochondrial DNA heteroplasmies in Huntington's disease.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Purine Nucleotides Metabolism and Signaling in Huntington's Disease: Search for a Target for Novel Therapies.International journal of molecular sciences · 2021Review
- Propensity for somatic expansion increases over the course of life in Huntington disease.eLife · 2021Article
- Mutant Huntingtin stalls ribosomes and represses protein synthesis in a cellular model of Huntington disease.Nature communications · 2021Article
- Mutant HTT (huntingtin) impairs mitophagy in a cellular model of Huntington disease.Autophagy · 2021Article
- Inositol hexakisphosphate kinase-2 determines cellular energy dynamics by regulating creatine kinase-B.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Potential role of TrkB agonist in neuronal survival by promoting CREB/BDNF and PI3K/Akt signaling in vitro and in vivo model of 3-nitropropionic acid (3-NP)-induced neuronal death.Apoptosis : an international journal on programmed cell death · 2021Article
- Striatal Chloride Dysregulation and Impaired GABAergic Signaling Due to Cation-Chloride Cotransporter Dysfunction in Huntington's Disease.Frontiers in cellular neuroscience · 2021Review
- D1R- and D2R-Medium-Sized Spiny Neurons Diversity: Insights Into Striatal Vulnerability to Huntington's Disease Mutation.Frontiers in cellular neuroscience · 2021Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 2 countries.
Funding
Abstract
Brain energy deficit has been a suggested cause of Huntington disease (HD), but ATP depletion has not reliably been shown in preclinical models, possibly because of the immediate post-mortem changes in cellular energy metabolism. To examine a potential role of a low energy state in HD, we measured, for the first time in a neurodegenerative model, brain levels of high energy phosphates using microwave fixation, which instantaneously inactivates brain enzymatic activities and preserves in vivo levels of analytes. We studied HD transgenic R6/2 mice at ages 4, 8, and 12 weeks. We found significantly increased creatine and phosphocreatine, present as early as 4 weeks for phosphocreatine, preceding motor system deficits and decreased ATP levels in striatum, hippocampus, and frontal cortex of R6/2 mice. ATP and phosphocreatine concentrations were inversely correlated with the number of CAG repeats. Conversely, in mice injected with 3-nitroproprionic acid, an acute model of brain energy deficit, both ATP and phosphocreatine were significantly reduced. Increased creatine and phosphocreatine in R6/2 mice was associated with decreased guanidinoacetate N-methyltransferase and creatine kinase, both at the protein and RNA levels, and increased phosphorylated AMP-dependent protein kinase (pAMPK) over AMPK ratio. In addition, in 4-month-old knock-in Hdh(Q111/+) mice, the earliest metabolic alterations consisted of increased phosphocreatine in the frontal cortex and increased the pAMPK/AMPK ratio. Altogether, this study provides the first direct evidence of chronic alteration in homeostasis of high energy phosphates in HD models in the earliest stages of the disease, indicating possible reduced utilization of the brain phosphocreatine pool.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.