Article
Neurosciences
Jens Andersen, Sofie K. Christensen, Emil W. Westi, Marta Diaz-delCastillo, Heikki Tanila, Arne Schousboe, Blanca Aldana, Helle S. Waagepetersen
Summary: This study found that in Alzheimer's disease (AD), there is prominent neuronal hypometabolism in the hippocampal slices of affected mice, while a reduction in glutamine synthesis in astrocytes directly impedes neuronal GABA synthesis.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Anesthesiology
Qin-qin He, Man Yang, Jing Huang, Wei Wu, Kuo Tang, Yong Zhang, Jian Zhou, Wei Ou, Maodi Xie, Yu Liang, Peilin Lu, Yunxia Zuo, Hai Yu, Tao Li
Summary: Intermittent hypoxia exposure decreased mouse sensitivity to sevoflurane anesthesia through enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain, as shown by the experimental results.
BRITISH JOURNAL OF ANAESTHESIA
(2022)
Review
Biochemistry & Molecular Biology
Go Woon Kim, Dong Hoon Lee, Yu Hyun Jeon, Jung Yoo, So Yeon Kim, Sang Wu Lee, Ha Young Cho, So Hee Kwon
Summary: Glutamine plays a crucial role in cancer metabolism, with cancer cells consuming excessive amounts for rapid proliferation, especially in poorly vascularized cancers. Glutamine synthetase (GS) is essential in cancer metabolism as the sole enzyme responsible for synthesizing glutamine, which supports nucleotide synthesis. GS exhibits pro-tumoral features by providing glutamine to cancer cells in the tumor microenvironment, enabling cancer cells to maintain sufficient glutamine levels for catabolism, ultimately supporting cancer cell proliferation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Plant Sciences
Kim-Teng Lee, Hong-Sheng Liao, Ming-Hsiun Hsieh
Summary: Glutamine (Gln) is the first synthesized amino acid in plant nitrogen assimilation. Glutamine synthetase (GS), an ancient enzyme, converts glutamate (Glu) and NH4+ into Gln at the expense of ATP. Plants have multiple GS isoenzymes that ensure sufficient Gln supply for growth and development. Gln serves as a building block for protein synthesis and as a nitrogen donor for the biosynthesis of various molecules.
PLANT AND CELL PHYSIOLOGY
(2023)
Article
Oncology
Robert Schoeppe, Nathalie Babl, Sonja-Maria Decking, Gabriele Schoenhammer, Andreas Siegmund, Christina Bruss, Katja Dettmer, Peter J. Oefner, Linus Frick, Anna Weigert, Jonathan Jantsch, Wolfgang Herr, Michael Rehli, Kathrin Renner, Marina Kreutz
Summary: Glutamine synthetase (GS) is important for the survival of tumor cells in a glutamine deficient environment, but its impact on survival and function of myeloid cells is minimal except for the monocytic leukemia cell line THP-1. Inhibition of GS also targets immune cells such as dendritic cells (DCs) and macrophages, reducing their survival and reversing the proliferation rescue of THP-1 cells caused by glutamate supplementation.
FRONTIERS IN ONCOLOGY
(2023)
Article
Clinical Neurology
Dana Marafi, Jawid M. Fatih, Rauan Kaiyrzhanov, Matteo P. Ferla, Charul Gijavanekar, Aljazi Al-Maraghi, Ning Liu, Emily Sites, Hessa S. Alsaif, Mohammad Al-Owain, Mohamed Zakkariah, Ehab El-Anany, Ulviyya Guliyeva, Sughra Guliyeva, Colette Gaba, Ateeq Haseeb, Amal M. Alhashem, Enam Danish, Vasiliki Karageorgou, Christian Beetz, Alaa A. Subhi, Sureni Mullegama, Erin Torti, Monisha Sebastin, Margo Sheck Breilyn, Susan Duberstein, Mohamed S. Abdel-Hamid, Tadahiro Mitani, Haowei Du, Jill A. Rosenfeld, Shalini N. Jhangiani, Zeynep Coban Akdemir, Richard A. Gibbs, Jenny C. Taylor, Khalid A. Fakhro, Jill Hunter, Davut Pehlivan, Maha S. Zaki, Joseph G. Gleeson, Reza Maroofian, Henry Houlden, Jennifer E. Posey, V. Reid Sutton, Fowzan S. Alkuraya, Sarah H. Elsea, James R. Lupski
Summary: SLC38A3 is a novel disease gene for developmental and epileptic encephalopathy, and the likely pathophysiology of the disease is perturbations in glutamine homeostasis.
Review
Cell Biology
Veronica Marabitti, Manuela Giansanti, Francesca De Mitri, Francesca Gatto, Angela Mastronuzzi, Francesca Nazio
Summary: Tumor-specific alterations in metabolism are crucial for sustaining cell growth and survival in various cancers, but the heterogeneous nature of metabolism poses challenges for effective anticancer therapies. Medulloblastoma is a highly heterogeneous pediatric brain tumor with complex intratumoral cellular diversity. This review highlights the mechanisms through which medulloblastoma cells rewire their metabolism and energy production networks to support rapid growth, resistance to stress, invasion, metastasis, and therapy. The potential clinical benefits of targeting energy metabolism in suppressing medulloblastoma progression and enhancing current therapies are also discussed.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Corinne S. Wilson, Preeti Dohare, Shaina Orbeta, Julia W. Nalwalk, Yunfei Huang, Russell J. Ferland, Rajan Sah, Annalisa Scimemi, Alexander A. Mongin
Summary: The knockout of the LRRC8A gene in mice leads to seizures in adolescence, as well as abnormalities in neurons and astrocytes in the brain. These abnormalities are associated with reactive astrogliosis, as well as dysregulation of amino acid neurotransmitter uptake and supply by astrocytes.
Article
Pharmacology & Pharmacy
Chuqiao Pan, Shijie Mao, Zeping Xiong, Zhao Chen, Ning Xu
Summary: Glutamate dehydrogenase (GDH) is a key enzyme in mammalian glutamate metabolism, participating in multiple metabolic pathways and cellular activities. Its dysfunction may lead to various neurodegenerative diseases. Activators and gene therapy targeting GDH have shown potential in protecting neurons and improving motor disorders caused by glutamate metabolism disorders. This approach offers new insights and treatment strategies for neurodegenerative diseases.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Plant Sciences
Yihao Wei, Shuping Xiong, Zhiyong Zhang, Xiaodan Meng, Lulu Wang, Xiaojiao Zhang, Meiqin Yu, Haidong Yu, Xiaochun Wang, Xinming Ma
Summary: This study investigated the localization and expression of individual TaGS isozymes in wheat grain, highlighting the distinct roles they play in nitrogen metabolism during grain development. TaGS1;3 was found to play a key role in Gln assimilation into endosperm for gluten synthesis, with stable expression in specific grain tissues. The findings suggest that GS-GOGAT cycle and GDH have varying impacts on NH4+ assimilation in different stages of grain development.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Psychiatry
S. Andrea Wijtenburg, Min Wang, Stephanie A. Korenic, Shuo Chen, Peter B. Barker, Laura M. Rowland
Summary: Proton magnetic resonance spectroscopy (MRS) studies in schizophrenia have revealed altered GABAergic, glutamatergic, and bioenergetic pathways, with multi-region differences observed between subjects with schizophrenia, first-degree relatives, and healthy controls using 7T MRS. These differences suggest potential genetic vulnerability and evolution with illness duration, not solely attributed to antipsychotic interventions.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Endocrinology & Metabolism
Narayan D. Soni, Akila Ramesh, Dipak Roy, Anant B. Patel
Summary: Alzheimer's disease is a common neurodegenerative disorder, and the ICV-STZ model exhibits typical neurometabolic deficits observed in AD, suggesting its utility in understanding the mechanism of sporadic AD.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Endocrinology & Metabolism
Yury Koush, Robin A. de Graaf, Ron Kupers, Laurence Dricot, Maurice Ptito, Kevin L. Behar, Douglas L. Rothman, Fahmeed Hyder
Summary: Functional MRI can identify activated and deactivated brain regions in task paradigms, with changes in these patterns observed in diseases, leading to research into their biochemical and biophysical mechanisms. The study investigated metabolic differences in activated and deactivated brain regions, finding that BOLD responses are impacted oppositely by task-induced inhibition, and increases in aerobic glycolysis and glutamatergic activity distinguish the BOLD response in (de)activated areas.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Agronomy
Huayan Yin, Fan Yang, Xiaoyan He, Xuye Du, Ping Mu, Wujun Ma
Summary: This review article examines the regulatory role of plant glutamine synthetase (GS) and its molecular mechanism in mitigating stress injury, focusing on the function of plant GS in stress tolerance response. The review aims to provide a reference for the utilization of plant GS in crop stress tolerance breeding.
Article
Biochemistry & Molecular Biology
Veronica Rodriguez-Herrero, Arnau Peris, Monica Camacho, Vanesa Bautista, Julia Esclapez, Maria-Jose Bonete
Summary: The study uncovers a new metabolic pathway in halophilic archaea, expanding the understanding of alternative nitrogen source utilization in this domain.
Article
Biochemical Research Methods
Michael Sorensen, Anne Byriel Walls, Gitte Dam, Lasse Kristoffer Bak, Jens Velde Andersen, Peter Ott, Hendrik Vilstrup, Arne Schousboe
Summary: Hepatic encephalopathy is a neuropsychiatric complication of liver failure, characterized by reduced brain energy metabolism. This reduction is likely caused by elevated GABA levels due to increased synthesis of glutamine in astrocytes for ammonia detoxification.
ANALYTICAL BIOCHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Jens Andersen, Arne Schousboe
Summary: Glutamine plays an essential role in cerebral metabolism, including ammonia homeostasis, energy metabolism, and neurotransmitter recycling. The balance of cerebral glutamine is regulated by the metabolic coupling of neurons and astrocytes, and disruptions in this balance are associated with various neurological diseases. Decreased astrocyte glutamine synthesis can lead to a deficiency in metabolic substrates and precursors for neurotransmitter synthesis in neurons, resulting in synaptic dysfunction.
NEUROCHEMICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Jens Andersen, Emil W. Westi, Elliott S. Neal, Blanca Aldana, Karin Borges
Summary: Ketogenic diets and medium-chain triglycerides play important roles in the treatment of neurological disorders, with their metabolites serving as auxiliary brain fuels in different cell types without notable competition.
NEUROCHEMICAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Jens V. Andersen, Arne Schousboe, Petrine Wellendorph
Summary: Synaptic regulation of GABA, the primary inhibitory neurotransmitter, is crucial for brain function. Astrocytes play fundamental roles in regulating synaptic GABA signaling by removing excess GABA from the synapse and using it as a metabolic substrate for glutamine synthesis. The flow of GABA and glutamine between neurons and astrocytes, known as the GABA-glutamine cycle, is essential for maintaining inhibitory signaling.
ESSAYS IN BIOCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Jens V. Andersen, Arne Schousboe
Summary: Since the recognition of glutamate and GABA as principal neurotransmitters, significant discoveries have been made about their synaptic homeostasis. The glutamate/GABA-glutamine cycle, involving the recycling between neurons and astrocytes, plays a crucial role in maintaining synaptic transmission. The metabolic function of neurons and astrocytes is closely related to the glutamate/GABA-glutamine cycle, with astrocytes providing metabolic support for neurons. The review focuses on cellular uptake, metabolism, and recycling of glutamate and GABA, as well as their role in brain pathology and the potential of targeting astrocyte metabolism for intervention.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Gerald A. Dienel, Arne Schousboe, Mary C. McKenna, Douglas L. Rothman
Summary: Leif Hertz made significant contributions to the understanding of astrocyte metabolism and signaling in the brain, and his work has had a high impact on the field of energy metabolism.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jens V. Andersen, Emil W. Westi, Nane Griem-Krey, Niels H. Skotte, Arne Schousboe, Blanca I. Aldana, Petrine Wellendorph
Summary: This study investigated the role of CaMKIIa in brain energy and neurotransmitter metabolism using a genetic knockout mouse model. The results showed that the oxidative metabolism of glucose in the cerebral cortex was significantly reduced in the absence of CaMKIIa, while the metabolism of acetate, primarily reflecting astrocyte metabolism, was unaffected. Additionally, the metabolism of glutamate in the excitatory system was impaired, while the metabolism of GABA was unaffected. These findings suggest that CaMKIIa signaling plays a metabolic role in cellular energy and neurotransmitter metabolism in the brain.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Neurosciences
Emil W. Westi, Jens Andersen, Blanca I. Aldana
Summary: Disrupted brain metabolism is crucial for neurodegenerative diseases, and the energy metabolism of neurons and astrocytes through the glutamate/GABA-glutamine cycle plays a vital role in neurotransmitter recycling. Isotope tracing, a technique to monitor cellular metabolism, has helped elucidate the mechanistic involvement of altered brain metabolism in disease progression. This review discusses the advantages, drawbacks, and applications of isotope tracing in different cerebral preparations and narrates how it has facilitated the discovery of central metabolic features in neurodegeneration, particularly in the metabolic cooperation between neurons and astrocytes.
NEUROBIOLOGY OF DISEASE
(2023)
Editorial Material
Neurosciences
Olaf B. Paulson, Arne Schousboe, Hans Hultborn
Summary: The history of Danish neuroscience dates back to the 17th century, with the first Danish neuroscientist, Thomas Bartholin. Danish neuroscience has always been connected to clinical disciplines. In the 20th century, basic neuroscience developed rapidly, while clinical neuroscience continued and saw important translational research and collaboration with basic neuroscience.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Laura Mikel Mcnair, Jens Velde Andersen, Helle Sonderby Waagepetersen
Summary: This study reveals fundamental alterations in cellular energy and neurotransmitter metabolism in the aging brain, which may contribute to age-related hippocampal deficits.
NEUROCHEMISTRY INTERNATIONAL
(2023)