ArticleMetallomics : integrated biometal science2015
Untargeted metabolic profiling identifies interactions between Huntington's disease and neuronal manganese status.
Article in Metallomics : integrated biometal science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
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- The Impact of Elevated Atmospheric Carbon Dioxide Exposure on Magic Tomatoes' Nutrition-Health Properties.International journal of molecular sciences · 2023Article
- A genetically encoded fluorescent sensor for manganese(II), engineered from lanmodulin.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Metabolomic Biomarkers Are Associated With Area of the Pons in Fragile X Premutation Carriers at Risk for Developing FXTAS.Frontiers in psychiatry · 2021Article
- Dilute-and-shoot-based direct nano-electrospray ionization tandem mass spectrometry as screening methodology for multivitamins in dietary supplement and human urine.Journal of advanced research · 2020Article
- Manganese-induced neurodegenerative diseases and possible therapeutic approaches.Expert review of neurotherapeutics · 2020Review
- Metabolic basis of neuronal vulnerability to ischemia; an in vivo untargeted metabolomics approach.Scientific reports · 2020Article
- Metabolomic Responses to Manganese Dose in SH-SY5Y Human Neuroblastoma Cells.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Manganese-Induced Neurotoxicity: New Insights Into the Triad of Protein Misfolding, Mitochondrial Impairment, and Neuroinflammation.Frontiers in neuroscience · 2019Review
- Transcriptome Analysis Reveals Distinct Responses to PhysiologicFrontiers in genetics · 2019Article
- The Use of Metabolomics to Identify Biological Signatures of Manganese Exposure.Annals of work exposures and health · 2017Article
- Metabolic profiling of presymptomatic Huntington's disease sheep reveals novel biomarkers.Scientific reports · 2017Article
- "Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies".BMC pharmacology & toxicology · 2016Review
- Fatty Acid Binding Protein 5 Modulates Docosahexaenoic Acid-Induced Recovery in Rats Undergoing Spinal Cord Injury.Journal of neurotrauma · 2016Article
- Targeting the untargeted in molecular phenomics with structurally-selective ion mobility-mass spectrometry.Current opinion in biotechnology · 2016Review
- Neonatal Iron Supplementation Induces Striatal Atrophy in Female YAC128 Huntington's Disease Mice.Journal of Huntington's disease · 2016Article
- Changes in Brain Metallome/Metabolome Pattern due to a Single i.v. Injection of Manganese in Rats.PloS one · 2015Article
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Manganese (Mn) is an essential micronutrient for development and function of the nervous system. Deficiencies in Mn transport have been implicated in the pathogenesis of Huntington's disease (HD), an autosomal dominant neurodegenerative disorder characterized by loss of medium spiny neurons of the striatum. Brain Mn levels are highest in striatum and other basal ganglia structures, the most sensitive brain regions to Mn neurotoxicity. Mouse models of HD exhibit decreased striatal Mn accumulation and HD striatal neuron models are resistant to Mn cytotoxicity. We hypothesized that the observed modulation of Mn cellular transport is associated with compensatory metabolic responses to HD pathology. Here we use an untargeted metabolomics approach by performing ultraperformance liquid chromatography-ion mobility-mass spectrometry (UPLC-IM-MS) on control and HD immortalized mouse striatal neurons to identify metabolic disruptions under three Mn exposure conditions, low (vehicle), moderate (non-cytotoxic) and high (cytotoxic). Our analysis revealed lower metabolite levels of pantothenic acid, and glutathione (GSH) in HD striatal cells relative to control cells. HD striatal cells also exhibited lower abundance and impaired induction of isobutyryl carnitine in response to increasing Mn exposure. In addition, we observed induction of metabolites in the pentose shunt pathway in HD striatal cells after high Mn exposure. These findings provide metabolic evidence of an interaction between the HD genotype and biologically relevant levels of Mn in a striatal cell model with known HD by Mn exposure interactions. The metabolic phenotypes detected support existing hypotheses that changes in energetic processes underlie the pathobiology of both HD and Mn neurotoxicity.
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