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  1. Book: Brain energy metabolism

    Hirrlinger, Johannes / Waagepetersen, Helle S.

    (Neuromethods ; 90 ; Springer protocols)

    2014  

    Author's details ed. by Johannes Hirrlinger ; Helle S. Waagepetersen
    Series title Neuromethods ; 90
    Springer protocols
    Collection
    Keywords Brain/Metabolism ; Energy metabolism
    Subject code 612.8042
    Language English
    Size XIV, 368 S. : Ill., graph. Darst., 27 cm
    Publisher Humana Press
    Publishing place New York
    Publishing country United States
    Document type Book
    Note Includes bibliographical references and index
    HBZ-ID HT018438780
    ISBN 978-1-4939-1058-8 ; 9781493910595 ; 1-4939-1058-2 ; 1493910590
    Database Catalogue ZB MED Medicine, Health

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    2014 A 4079 available for loan (reading room) Lesesaal EG

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  2. Article ; Online: Increased glucose metabolism and impaired glutamate transport in human astrocytes are potential early triggers of abnormal extracellular glutamate accumulation in hiPSC-derived models of Alzheimer's disease.

    Salcedo, Claudia / Pozo Garcia, Victoria / García-Adán, Bernat / Ameen, Aishat O / Gegelashvili, Georgi / Waagepetersen, Helle S / Freude, Kristine K / Aldana, Blanca I

    Journal of neurochemistry

    2023  

    Abstract: Glutamate recycling between neurons and astrocytes is essential to maintain neurotransmitter homeostasis. Disturbances in glutamate homeostasis, resulting in excitotoxicity and neuronal death, have been described as a potential mechanism in Alzheimer's ... ...

    Abstract Glutamate recycling between neurons and astrocytes is essential to maintain neurotransmitter homeostasis. Disturbances in glutamate homeostasis, resulting in excitotoxicity and neuronal death, have been described as a potential mechanism in Alzheimer's disease (AD) pathophysiology. However, glutamate neurotransmitter metabolism in different human brain cells, particularly astrocytes, has been poorly investigated at the early stages of AD. We sought to investigate glucose and glutamate metabolism in AD by employing human induced pluripotent stem cell (hiPSC)-derived astrocytes and neurons carrying mutations in the amyloid precursor protein (APP) or presenilin-1 (PSEN-1) gene as found in familial types of AD (fAD). Methods such as live-cell bioenergetics and metabolic mapping using [
    Language English
    Publishing date 2023-12-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 80158-6
    ISSN 1471-4159 ; 0022-3042 ; 1474-1644
    ISSN (online) 1471-4159
    ISSN 0022-3042 ; 1474-1644
    DOI 10.1111/jnc.16014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Astrocytic pyruvate carboxylation: Status after 35 years.

    Schousboe, Arne / Waagepetersen, Helle S / Sonnewald, Ursula

    Journal of neuroscience research

    2019  Volume 97, Issue 8, Page(s) 890–896

    Abstract: The first two publications dealing with the question of the cellular localization of the enzyme pyruvate carboxylase (PC) which in the brain represents the most important metabolic pathway to allow anaplerosis of TCA cycle constituents were published in ... ...

    Abstract The first two publications dealing with the question of the cellular localization of the enzyme pyruvate carboxylase (PC) which in the brain represents the most important metabolic pathway to allow anaplerosis of TCA cycle constituents were published in 1983 and 1985. Hence, 2018 marks the 35th anniversary of the notion based on the results of the publications provided above that PC-catalyzed anaplerosis in the brain is an astrocytic process. This review will provide the background for investigating this enzymatic pathway as well as a discussion of cataplerosis, the degradation of products from anaplerosis, and the current status of the functional significance of pyruvate carboxylation in brain metabolism.
    MeSH term(s) Animals ; Astrocytes/metabolism ; Brain/metabolism ; Citric Acid Cycle ; Humans ; Neurons/metabolism ; Pyruvate Carboxylase/metabolism ; Pyruvic Acid/metabolism
    Chemical Substances Pyruvic Acid (8558G7RUTR) ; Pyruvate Carboxylase (EC 6.4.1.1)
    Language English
    Publishing date 2019-02-23
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 195324-2
    ISSN 1097-4547 ; 0360-4012
    ISSN (online) 1097-4547
    ISSN 0360-4012
    DOI 10.1002/jnr.24402
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Two Metabolic Fuels, Glucose and Lactate, Differentially Modulate Exocytotic Glutamate Release from Cultured Astrocytes.

    Montana, Vedrana / Flint, Daniel / Waagepetersen, Helle S / Schousboe, Arne / Parpura, Vladimir

    Neurochemical research

    2021  Volume 46, Issue 10, Page(s) 2551–2579

    Abstract: Astrocytes have a prominent role in metabolic homeostasis of the brain and can signal to adjacent neurons by releasing glutamate via a process of regulated exocytosis. Astrocytes synthesize glutamate de novo owing to the pyruvate entry to the citric/ ... ...

    Abstract Astrocytes have a prominent role in metabolic homeostasis of the brain and can signal to adjacent neurons by releasing glutamate via a process of regulated exocytosis. Astrocytes synthesize glutamate de novo owing to the pyruvate entry to the citric/tricarboxylic acid cycle via pyruvate carboxylase, an astrocyte specific enzyme. Pyruvate can be sourced from two metabolic fuels, glucose and lactate. Thus, we investigated the role of these energy/carbon sources in exocytotic glutamate release from astrocytes. Purified astrocyte cultures were acutely incubated (1 h) in glucose and/or lactate-containing media. Astrocytes were mechanically stimulated, a procedure known to increase intracellular Ca
    MeSH term(s) Animals ; Astrocytes/metabolism ; Calcium/metabolism ; Exocytosis/physiology ; Glucose/metabolism ; Glutamic Acid/metabolism ; Lactic Acid/metabolism ; Proteome/metabolism ; Proteomics ; Rats, Sprague-Dawley ; Rats
    Chemical Substances Proteome ; Lactic Acid (33X04XA5AT) ; Glutamic Acid (3KX376GY7L) ; Glucose (IY9XDZ35W2) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2021-05-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 199335-5
    ISSN 1573-6903 ; 0364-3190
    ISSN (online) 1573-6903
    ISSN 0364-3190
    DOI 10.1007/s11064-021-03340-y
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  5. Book: Brain energy metabolism

    Hirrlinger, Johannes / Waagepetersen, Helle S

    (Neuromethods, ; v. 90 ; Springer Protocols,)

    2014  

    Author's details edited by Johannes Hirrlinger, Helle S. Waagepetersen
    Series title Neuromethods, ; v. 90
    Springer Protocols,
    MeSH term(s) Brain Chemistry/physiology ; Brain/metabolism ; Energy Metabolism
    Language English
    Size 370 pages :, illustrations
    Document type Book
    ISBN 9781493910588 ; 1493910582 ; 9781493910595 ; 1493910590
    Database Catalogue of the US National Library of Medicine (NLM)

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  6. Article ; Online: Rates of pyruvate carboxylase, glutamate and GABA neurotransmitter cycling, and glucose oxidation in multiple brain regions of the awake rat using a combination of [2-

    McNair, Laura M / Mason, Graeme F / Chowdhury, Golam Mi / Jiang, Lihong / Ma, Xiaoxian / Rothman, Douglas L / Waagepetersen, Helle S / Behar, Kevin L

    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

    2022  Volume 42, Issue 8, Page(s) 1507–1523

    Abstract: Anaplerosis occurs predominately in astroglia through the action of pyruvate carboxylase (PC). The rate of PC (Vpc) has been reported for cerebral cortex (or whole brain) of awake humans and anesthetized rodents, but regional brain rates remain largely ... ...

    Abstract Anaplerosis occurs predominately in astroglia through the action of pyruvate carboxylase (PC). The rate of PC (Vpc) has been reported for cerebral cortex (or whole brain) of awake humans and anesthetized rodents, but regional brain rates remain largely unknown and, hence, were subjected to investigation in the current study. Awake male rats were infused with either [2-
    MeSH term(s) Animals ; Brain/metabolism ; Carbon Isotopes/metabolism ; Glucose/metabolism ; Glutamic Acid/metabolism ; Glutamine/metabolism ; Male ; Neurons/metabolism ; Neurotransmitter Agents/metabolism ; Pyruvate Carboxylase/metabolism ; Rats ; Wakefulness ; gamma-Aminobutyric Acid/metabolism
    Chemical Substances Carbon Isotopes ; Neurotransmitter Agents ; Glutamine (0RH81L854J) ; Glutamic Acid (3KX376GY7L) ; gamma-Aminobutyric Acid (56-12-2) ; Pyruvate Carboxylase (EC 6.4.1.1) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2022-01-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 604628-9
    ISSN 1559-7016 ; 0271-678X
    ISSN (online) 1559-7016
    ISSN 0271-678X
    DOI 10.1177/0271678X221074211
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Proteomic phenotype of cerebral organoids derived from autism spectrum disorder patients reveal disrupted energy metabolism, cellular components, and biological processes.

    Ilieva, Mirolyuba / Aldana, Blanca Irene / Vinten, Kasper Tore / Hohmann, Sonja / Woofenden, Thomas William / Lukjanska, Renate / Waagepetersen, Helle S / Michel, Tanja Maria

    Molecular psychiatry

    2022  Volume 27, Issue 9, Page(s) 3749–3759

    Abstract: The way in which brain morphology and proteome are remodeled during embryonal development, and how they are linked to the cellular metabolism, could be a key for elucidating the pathological mechanisms of certain neurodevelopmental disorders. Cerebral ... ...

    Abstract The way in which brain morphology and proteome are remodeled during embryonal development, and how they are linked to the cellular metabolism, could be a key for elucidating the pathological mechanisms of certain neurodevelopmental disorders. Cerebral organoids derived from autism spectrum disorder (ASD) patients were generated to capture critical time-points in the neuronal development, and metabolism and protein expression were investigated. The early stages of development, when neurogenesis commences (day in vitro 39), appeared to be a critical timepoint in pathogenesis. In the first month of development, increased size in ASD-derived organoids were detected in comparison to the controls. The size of the organoids correlates with the number of proliferating cells (Ki-67 positive cells). A significant difference in energy metabolism and proteome phenotype was also observed in ASD organoids at this time point, specifically, prevalence of glycolysis over oxidative phosphorylation, decreased ATP production and mitochondrial respiratory chain activity, differently expressed cell adhesion proteins, cell cycle (spindle formation), cytoskeleton, and several transcription factors. Finally, ASD patients and controls derived organoids were clustered based on a differential expression of ten proteins-heat shock protein 27 (hsp27) phospho Ser 15, Pyk (FAK2), Elk-1, Rac1/cdc42, S6 ribosomal protein phospho Ser 240/Ser 244, Ha-ras, mTOR (FRAP) phospho Ser 2448, PKCα, FoxO3a, Src family phospho Tyr 416-at day 39 which could be defined as potential biomarkers and further investigated for potential drug development.
    MeSH term(s) Humans ; Organoids ; Autism Spectrum Disorder/genetics ; Proteomics ; Proteome/genetics ; Phenotype ; Biological Phenomena ; Energy Metabolism
    Chemical Substances Proteome
    Language English
    Publishing date 2022-05-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1330655-8
    ISSN 1476-5578 ; 1359-4184
    ISSN (online) 1476-5578
    ISSN 1359-4184
    DOI 10.1038/s41380-022-01627-2
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  8. Article ; Online: Distinct differences in rates of oxygen consumption and ATP synthesis of regionally isolated non-synaptic mouse brain mitochondria.

    Andersen, Jens V / Jakobsen, Emil / Waagepetersen, Helle S / Aldana, Blanca I

    Journal of neuroscience research

    2019  Volume 97, Issue 8, Page(s) 961–974

    Abstract: Brain mitochondrial dysfunction has been implicated in several neurodegenerative diseases. The distribution and efficiency of mitochondria display large heterogeneity throughout the regions of the brain. This may imply that the selective regional ... ...

    Abstract Brain mitochondrial dysfunction has been implicated in several neurodegenerative diseases. The distribution and efficiency of mitochondria display large heterogeneity throughout the regions of the brain. This may imply that the selective regional susceptibility of neurodegenerative diseases could be mediated through inherent differences in regional mitochondrial function. To investigate regional cerebral mitochondrial energetics, the rates of oxygen consumption and adenosine-5'-triphosphate (ATP) synthesis were assessed in isolated non-synaptic mitochondria of the cerebral cortex, hippocampus, and striatum of the male mouse brain. Oxygen consumption rates were assessed using a Seahorse XFe96 analyzer and ATP synthesis rates were determined by an online luciferin-luciferase coupled luminescence assay. Complex I- and complex II-driven respiration and ATP synthesis, were investigated by applying pyruvate in combination with malate, or succinate, as respiratory substrates, respectively. Hippocampal mitochondria exhibited the lowest basal and adenosine-5'-diphosphate (ADP)-stimulated rate of oxygen consumption when provided pyruvate and malate. However, hippocampal mitochondria also exhibited an increased proton leak and an elevated relative rate of oxygen consumption in response to the uncoupler carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), showing a large capacity for uncoupled respiration in the presence of pyruvate. When the complex II-linked substrate succinate was provided, striatal mitochondria exhibited the highest respiration and ATP synthesis rate, whereas hippocampal mitochondria had the lowest. However, the mitochondrial efficiency, determined as ATP produced/O
    MeSH term(s) Adenosine Triphosphate/metabolism ; Animals ; Animals, Outbred Strains ; Brain/metabolism ; Cerebral Cortex/metabolism ; Corpus Striatum/metabolism ; Hippocampus/metabolism ; Male ; Mice ; Mitochondria/metabolism ; Oxygen Consumption
    Chemical Substances Adenosine Triphosphate (8L70Q75FXE)
    Language English
    Publishing date 2019-01-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 195324-2
    ISSN 1097-4547 ; 0360-4012
    ISSN (online) 1097-4547
    ISSN 0360-4012
    DOI 10.1002/jnr.24371
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Effects of diabetes on brain metabolism--is brain glycogen a significant player?

    Sickmann, Helle M / Waagepetersen, Helle S

    Metabolic brain disease

    2014  Volume 30, Issue 1, Page(s) 335–343

    Abstract: Brain glycogen, being an intracellular glucose reservoir, contributes to maintain energy and neurotransmitter homeostasis under physiological as well as pathological conditions. Under conditions with a disturbance in systemic glucose metabolism such as ... ...

    Abstract Brain glycogen, being an intracellular glucose reservoir, contributes to maintain energy and neurotransmitter homeostasis under physiological as well as pathological conditions. Under conditions with a disturbance in systemic glucose metabolism such as in diabetes, the supply of glucose to the brain may be affected and have important impacts on brain metabolism and neurotransmission. This also implies that brain glycogen may serve an essential role in the diabetic state to sustain appropriate brain function. There are two main types of diabetes; type 1 and type 2 diabetes and both types may be associated with brain impairments e.g. cognitive decline and dementia. It is however, not clear how these impairments on brain function are linked to alterations in brain energy and neurotransmitter metabolism. In this review, we will illuminate how rodent diabetes models have contributed to a better understanding of how brain energy and neurotransmitter metabolism is affected in diabetes. There will be a particular focus on the role of brain glycogen to support glycolytic and TCA cycle activity as well as glutamate-glutamine cycle in type 1 and type 2 diabetes.
    MeSH term(s) Animals ; Astrocytes/metabolism ; Biological Transport ; Blood-Brain Barrier ; Brain/metabolism ; Citric Acid Cycle ; Diabetes Mellitus/metabolism ; Diabetes Mellitus, Experimental/metabolism ; Energy Metabolism ; Glucose/metabolism ; Glutamic Acid/metabolism ; Glutamine/metabolism ; Glycogen/metabolism ; Glycolysis ; Humans ; Lactates/metabolism ; Models, Biological ; Models, Neurological ; Neurons/metabolism ; Rats
    Chemical Substances Lactates ; Glutamine (0RH81L854J) ; Glutamic Acid (3KX376GY7L) ; Glycogen (9005-79-2) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2014-04-29
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 632824-6
    ISSN 1573-7365 ; 0885-7490
    ISSN (online) 1573-7365
    ISSN 0885-7490
    DOI 10.1007/s11011-014-9546-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Astrocytic glycogen metabolism in the healthy and diseased brain.

    Bak, Lasse K / Walls, Anne B / Schousboe, Arne / Waagepetersen, Helle S

    The Journal of biological chemistry

    2018  Volume 293, Issue 19, Page(s) 7108–7116

    Abstract: The brain contains a fairly low amount of glycogen, mostly located in astrocytes, a fact that has prompted the suggestion that glycogen does not have a significant physiological role in the brain. However, glycogen metabolism in astrocytes is essential ... ...

    Abstract The brain contains a fairly low amount of glycogen, mostly located in astrocytes, a fact that has prompted the suggestion that glycogen does not have a significant physiological role in the brain. However, glycogen metabolism in astrocytes is essential for several key physiological processes and is adversely affected in disease. For instance, diminished ability to break down glycogen impinges on learning, and epilepsy, Alzheimer's disease, and type 2 diabetes are all associated with abnormal astrocyte glycogen metabolism. Glycogen metabolism supports astrocytic K
    MeSH term(s) Alzheimer Disease/metabolism ; Animals ; Astrocytes/metabolism ; Brain/metabolism ; Calcium/metabolism ; Cyclic AMP/metabolism ; Diabetes Mellitus, Type 2/metabolism ; Glutamine/biosynthesis ; Glycogen/metabolism ; Glycogen Phosphorylase/metabolism ; Humans ; Isoenzymes/metabolism ; Learning/physiology ; Memory/physiology ; Neurotransmitter Agents/metabolism ; Potassium/metabolism ; Signal Transduction ; Sleep/physiology
    Chemical Substances Isoenzymes ; Neurotransmitter Agents ; Glutamine (0RH81L854J) ; Glycogen (9005-79-2) ; Cyclic AMP (E0399OZS9N) ; Glycogen Phosphorylase (EC 2.4.1.-) ; Potassium (RWP5GA015D) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2018-03-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.R117.803239
    Database MEDical Literature Analysis and Retrieval System OnLINE

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