Neuroscience in Denmark
Back to overview
General informationName (center, department, group or other)
10. May 2016
(Last edited: 1. March 2018)
Brief description of research activitiesHow are brain cells regulating their energy metabolism?
How are neuroransmitter pools of glutamate and GABA maintained?
How are neurotransmitter homeostasis and brain energy metabolism affected in Alzheimers disease and Type 2 diabetes ?
... and how may we manipulate these pharmacologically?
These are the four questions driving research in NeuroMet
The research in NeuroMet is focused on energy and amino acid metabolism in the mammalian brain. Primary mouse cell culture systems of neurons and astrocytes from cerebral cortex or cerebellum are extensively employed. In addition, genetically modified animals, organotypical hippocampal cultures, acutely isolated brain tissue, isolated mitochondria and cell lines are applied as model systems. An array of 3H, 15N and 13C isotopes is utilized in the mapping of metabolic pathways and their regulation. HPLC, mass spectrometry and are key analytical tools combined with biochemical assays.
KeywordsEnergy, glucose, Alzheimers, diabetes, astrocytes, glutamate, TCA cycle, amino acids, glycogen, hepatic encephalopathy
Research tools and techniquesmass spectrometry for metabolic mapping
13C H NMR for metabolic mapping
primary cultures of neurons and astrocytes
Scientific PersonnelNo of Associate Professors/Postdocs: 3
No of PhD students: 3
Key references from within the last 5 years1. Zhang Y, Schmid B, Nikolaisen NK, Rasmussen MA, Aldana BI, Agger M, Calloe K, Stummann TC, Larsen HM, Nielsen TT, Huang J, Xu F, Liu X, Bolund L, Meyer M, Bak LK, Waagepetersen HS, Luo Y, Nielsen JE; FReJA Consortium., Holst B, Clausen C,Hyttel P, Freude KK. Patient iPSC-Derived Neurons for Disease Modeling of Frontotemporal Dementia with Mutation in CHMP2B. Stem Cell Reports 2017. 8(3):648-658
2. Andersen JV, Christensen SK, Nissen JD, Waagepetersen HS. Improved cerebral energetics and ketone body metabolism in db/db mice. J. of Cerebral Blood Flow and Met. 2017.
3. Nissen JD, Lykke K, Bryk J, Stridh MH, Zaganas I, Skytt DM, Schousboe A, Bak LK, Enard W, Pääbo S, Waagepetersen HS. Expression of the human isoform of glutamate dehydrogenase, hGDH2, augments TCA cycle capacity and oxidative metabolism of glutamate during glucose deprivation in astrocytes, GLIA 2017. 65(3):474-488
4. Koivisto, H, Leinonen, H, Puurula, M, Hafez, HS, Barrera, GA, Stridh, MH, Waagepetersen, HS, Tiainen, M, Soininen, P, Zilberter, Y, and Tanila, H. Chronic Pyruvate Supplementation Increases Exploratory Activity and Brain Energy Reserves in Young and Middle-Aged Mice. Front Aging Neurosci, 2016. 8: p. 41.
5. Nissen, JD, Pajecka, K, Stridh, MH, Skytt, DM, and Waagepetersen, HS. Dysfunctional TCA-Cycle Metabolism in Glutamate Dehydrogenase Deficient Astrocytes. Glia, 2015. 63(12): p. 2313-26.
6. Muller, MS, Pedersen, SE, Walls, AB, Waagepetersen, HS, and Bak, LK. Isoform-selective regulation of glycogen phosphorylase by energy deprivation and phosphorylation in astrocytes. Glia, 2015. 63(1): p. 154-62.
7. Karaca, M, Frigerio, F, Migrenne, S, Martin-Levilain, J, Skytt, DM, Pajecka, K, Martin-del-Rio, R, Gruetter, R, Tamarit-Rodriguez, J, Waagepetersen, HS, Magnan, C, and Maechler, P. GDH-Dependent Glutamate Oxidation in the Brain Dictates Peripheral Energy Substrate Distribution. Cell Rep, 2015. 13(2): p. 365-75.
8. Hertz, L, Chen, Y, and Waagepetersen, HS. Effects of ketone bodies in Alzheimer's disease in relation to neural hypometabolism, beta-amyloid toxicity, and astrocyte function. J Neurochem, 2015. 134(1): p. 7-20.
9. Walls, AB, Eyjolfsson, EM, Schousboe, A, Sonnewald, U, and Waagepetersen, HS. A subconvulsive dose of kainate selectively compromises astrocytic metabolism in the mouse brain in vivo. J Cereb Blood Flow Metab, 2014. 34(8): p. 1340-6.
10. Muller, MS, Fox, R, Schousboe, A, Waagepetersen, HS, and Bak, LK. Astrocyte glycogenolysis is triggered by store-operated calcium entry and provides metabolic energy for cellular calcium homeostasis. Glia, 2014. 62(4): p. 526-34.