Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Characterization of energy and neurotransmitter metabolism in cortical glutamatergic neurons derived from human induced pluripotent stem cells: A novel approach to study metabolism in human neurons

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Enhancement of Autophagy and Solubilization of Ataxin-2 Alleviate Apoptosis in Spinocerebellar Ataxia Type 2 Patient Cells

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Early Intrathecal T Helper 17.1 Cell Activity in Huntington Disease

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Hereditære ataksier og sygdomme i det motoriske neuron

    Publikation: Bidrag til bog/antologi/rapportBidrag til bog/antologiUndervisning

  4. Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Peripheral neuropathy in hereditary spastic paraplegia caused by REEP1 variants

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Blanca I Aldana
  • Yu Zhang
  • Maria Fog Lihme
  • Lasse K Bak
  • Jørgen E Nielsen
  • Bjørn Holst
  • Poul Hyttel
  • Kristine K Freude
  • Helle S Waagepetersen
Vis graf over relationer

Alterations in the cellular metabolic machinery of the brain are associated with neurodegenerative disorders such as Alzheimer's disease. Novel human cellular disease models are essential in order to study underlying disease mechanisms. In the present study, we characterized major metabolic pathways in neurons derived from human induced pluripotent stem cells (hiPSC). With this aim, cultures of hiPSC-derived neurons were incubated with [U-13C]glucose, [U-13C]glutamate or [U-13C]glutamine. Isotopic labeling in metabolites was determined using gas chromatography coupled to mass spectrometry, and cellular amino acid content was quantified by high-performance liquid chromatography. Additionally, we evaluated mitochondrial function using real-time assessment of oxygen consumption via the Seahorse XFe96 Analyzer. Moreover, in order to validate the hiPSC-derived neurons as a model system, a metabolic profiling was performed in parallel in primary neuronal cultures of mouse cerebral cortex and cerebellum. These serve as well-established models of GABAergic and glutamatergic neurons, respectively. The hiPSC-derived neurons were previously characterized as being forebrain-specific cortical glutamatergic neurons. However, a comparable preparation of predominantly mouse cortical glutamatergic neurons is not available. We found a higher glycolytic capacity in hiPSC-derived neurons compared to mouse neurons and a substantial oxidative metabolism through the mitochondrial tricarboxylic acid (TCA) cycle. This finding is supported by the extracellular acidification and oxygen consumption rates measured in the cultured human neurons. [U-13C]Glutamate and [U-13C]glutamine were found to be efficient energy substrates for the neuronal cultures originating from both mice and humans. Interestingly, isotopic labeling in metabolites from [U-13C]glutamate was higher than that from [U-13C]glutamine. Although the metabolic profile of hiPSC-derived neurons in vitro was particularly similar to the profile of mouse cortical neurons, important differences between the metabolic profile of human and mouse neurons were observed. The results of the present investigation establish hallmarks of cellular metabolism in human neurons derived from iPSC.

OriginalsprogEngelsk
TidsskriftNeurochemistry International
Vol/bind106
Sider (fra-til)48-61
Antal sider14
ISSN0197-0186
DOI
StatusUdgivet - jun. 2017

ID: 52184642