Neuroscience in Denmark
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General informationName (center, department, group or other)
10. May 2016
Brief description of research activities
How 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: 2
Key references from within the last 5 years1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. Fries, AW, Dadsetan, S, Keiding, S, Bak, LK, Schousboe, A, Waagepetersen, HS, Simonsen, M, Ott, P, Vilstrup, H, and Sorensen, M. Effect of glutamine synthetase inhibition on brain and interorgan ammonia metabolism in bile duct ligated rats. J Cereb Blood Flow Metab, 2014. 34(3): p. 460-6.
9. Dam, G, Keiding, S, Munk, OL, Ott, P, Vilstrup, H, Bak, LK, Waagepetersen, HS, Schousboe, A, and Sorensen, M. Hepatic encephalopathy is associated with decreased cerebral oxygen metabolism and blood flow, not increased ammonia uptake. Hepatology, 2013. 57(1): p. 258-65.
10. Walls, AB, Eyjolfsson, EM, Smeland, OB, Nilsen, LH, Schousboe, I, Schousboe, A, Sonnewald, U, and Waagepetersen, HS. Knockout of GAD65 has major impact on synaptic GABA synthesized from astrocyte-derived glutamine. J Cereb Blood Flow Metab, 2011. 31(2): p. 494-503.