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
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.
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)
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
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)
Article
Clinical Neurology
Maxwell G. Farina, Mani Ratnesh S. Sandhu, Maxime Parent, Basavaraju G. Sanganahalli, Matthew Derbin, Roni Dhaher, Helen Wang, Hitten P. Zaveri, Yun Zhou, Niels C. Danbolt, Fahmeed Hyder, Tore Eid
Summary: The study successfully developed a method to precisely and specifically delete the GS gene in the postnatal brain, resulting in lower seizure thresholds, spontaneous recurrent seizures, and reduced functional connectivity.
Article
Immunology
Sharmely Sharon Ballon Romero, Lih-Jyh Fuh, Shih-Ya Hung, Yu-Chen Lee, Yu-Chuen Huang, Szu-Yu Chien, Yi-Hung Chen
Summary: This study aimed to investigate whether single or multiple dental pulp injuries induce persistent dental pain and their association with trigeminal central nociceptive pathways. The results showed that multiple dental pulp injuries resulted in persistent dental pain, while single dental pulp injury did not. Electroacupuncture treatment provided prolonged analgesic and neuroprotective effects.
FRONTIERS IN IMMUNOLOGY
(2023)
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)
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
Biochemistry & Molecular Biology
Duk-Shin Lee, Ji-Eun Kim
Summary: This study found that P2X7 receptor plays an important role in LPS-induced neuroinflammation by affecting Nrf2 activity/expression and GSH synthesis.
Article
Neurosciences
Emil W. Westi, Emil Jakobsen, Caroline M. Voss, Lasse K. Bak, Lars H. Pinborg, Blanca Aldana, Jens Andersen
Summary: Differences in cellular composition and structure may influence the metabolism of rodent and human brain. Human cerebral slices have lower metabolic rates but higher coupled respiration and more efficient mitochondrial coupling compared to mouse slices.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Cell Biology
Ya-Wen Xu, Jin-Shan Yang, De-Zhi Kang, Pei-Sen Yao
Summary: The study revealed that astrocytes can promote the astrocytic differentiation and glutamate uptake of GSCs via FPR activation, while differentiated GSCs exhibit lower proliferation ability compared to tumor cells.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2021)
Article
Plant Sciences
Ge Yan, Yujie Shi, Fangfang Chen, Chunsheng Mu, Junfeng Wang
Summary: This study investigated the physiological and metabolic mechanisms of perennial grass response to alkali stress using Leymus chinensis as the experimental material. The results showed that alkali stress inhibited seedling growth and photosynthesis, but increased nitrogen and ATP contents. Metabolic analysis revealed an increase in nucleotides, amino acids, and organic acids, while soluble sugar contents decreased under alkali stress. The glutamine synthetase/glutamate synthase (GS/GOGAT) cycle, associated with nitrogen metabolism, was the most significantly affected pathway. The study highlights the roles of amino acids, organic acids, nucleotides, and the GS/GOGAT cycle in the response of seedlings to alkali stress.
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)
Review
Clinical Neurology
Felix Chan, Judy Liu
Summary: Extensive research has shown a link between circadian rhythm and epilepsy, with various circadian genes implicated in epilepsy pathogenesis. Disruption of metabolic pathways regulated by these genes may mediate the circadian regulation of epilepsy, suggesting a novel therapeutic approach targeting circadian disruption in epilepsy.
Article
Clinical Neurology
Ana Belen Lopez-Rodriguez, Edel Hennessy, Carol L. Murray, Arshed Nazmi, Hugh J. Delaney, Daire Healy, Steven G. Fagan, Michael Rooney, Erika Stewart, Anouchka Lewis, Niamh de Barra, Philip Scarry, Louise Riggs-Miller, Delphine Boche, Mark O. Cunningham, Colm Cunningham
Summary: Neuroinflammation contributes to Alzheimer's disease progression, with secondary inflammatory insults potentially leading to delirium and accelerated cognitive decline. The presence of amyloid in the brain can make microglia, astrocytes, neurons, and cognition vulnerable to secondary inflammation, while infection can exacerbate neuroinflammatory cytokine synthesis. Investigating the exacerbation of neuroinflammation and its deleterious effects like delirium and disease progression in humans is warranted.
ALZHEIMERS & DEMENTIA
(2021)
Article
Endocrinology & Metabolism
Laura M. McNair, Graeme F. Mason, Golam M. Chowdhury, Lihong Jiang, Xiaoxian Ma, Douglas L. Rothman, Helle S. Waagepetersen, Kevin L. Behar
Summary: Anaplerosis, mediated by pyruvate carboxylase (PC) in astroglia, varies across different brain regions. The rate of PC contributes to oxidative glucose consumption and is positively correlated with glutamate/glutamine cycling.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Article
Cell Biology
Jens Andersen, Niels H. Skotte, Sofie K. Christensen, Filip S. Polli, Mohammad Shabani, Kia H. Markussen, Henriette Haukedal, Emil W. Westi, Marta Diaz-delCastillo, Ramon C. Sun, Kristi A. Kohlmeier, Arne Schousboe, Matthew S. Gentry, Heikki Tanila, Kristine K. Freude, Blanca Aldana, Matthias Mann, Helle S. Waagepetersen
Summary: Alzheimer's disease is characterized by cerebral amyloid-beta accumulation and cognitive decline, with changes in brain energy metabolism being important in early AD pathology. Neurons and astrocytes play a crucial role in metabolic collaboration, impacting neurotransmitter recycling at the synapse, but this area of study is still lacking in early AD development. The study reveals complex regional and cell-specific metabolic adaptations during the early stages of amyloid pathology, which may contribute to synaptic dysfunctions in AD progression.
CELL DEATH & DISEASE
(2021)
Article
Clinical Neurology
Gareth Morris, Elena Langa, Conor Fearon, Karen Conboy, Kelvin Lau E-How, Amaya Sanz-Rodriguez, Donncha F. O'Brien, Kieron Sweeney, Austin Lacey, Norman Delanty, Alan Beausang, Francesca M. Brett, Jane B. Cryan, Mark O. Cunningham, David C. Henshall
Summary: This study developed a testing platform for antimiRs using human brain tissue sections and demonstrated the effects of ant-134 on miR-134 in live human brain tissues. The findings support the preclinical development of a therapy targeting miR-134 and provide a flexible platform for testing antimiRs and other antisense oligonucleotide therapeutics in human brain.
Article
Biochemistry & Molecular Biology
Mirolyuba Ilieva, Blanca Irene Aldana, Kasper Tore Vinten, Sonja Hohmann, Thomas William Woofenden, Renate Lukjanska, Helle S. Waagepetersen, Tanja Maria Michel
Summary: The remodeling of brain morphology and proteome during embryonic development, along with its connection to cellular metabolism, could be crucial in understanding the pathological mechanisms of certain neurodevelopmental disorders. Cerebral organoids derived from autism spectrum disorder (ASD) patients were used to capture key moments in neuronal development and investigate metabolism and protein expression. The early stages of development, particularly when neurogenesis begins, were found to be critical in ASD pathogenesis. Differences in energy metabolism and proteome were observed, including increased glycolysis, decreased ATP production, and altered expression of cell adhesion proteins, cell cycle regulators, cytoskeletal proteins, and transcription factors. Furthermore, a cluster analysis based on differential protein expression identified potential biomarkers that could be explored for drug development.
MOLECULAR PSYCHIATRY
(2022)
Editorial Material
Neurosciences
Giovanna O. O. Nogueira, Patricia P. P. Garcez, Cedric Bardy, Mark O. O. Cunningham, Adriano Sebollela
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Cell Biology
Michael Spedding, Claude Sebban, Therese M. Jay, Cyril Rocher, Brigitte Tesolin-Decros, Paul Chazot, Esther Schenker, Gabor Szenasi, Gyorgy Levay, Katalin Megyeri, Jozsef Barkoczy, Laszlo G. Harsing, Ian Thomson, Mark O. Cunningham, Miles A. Whittington, Lori-An Etherington, Jeremy J. Lambert, Ferenc A. Antoni, Istvan Gacsalyi
Summary: Dysfunction in the H-PFC circuit is a critical factor in schizophrenia, and a new drug called EGIS 11150 has been found to induce theta rhythm, enhance H-PFC coherence, and restore long-term potentiation in this circuit. This suggests that phenotypical screening on H-PFC connectivity can uncover novel antipsychotics.
Article
Neurosciences
Maria Hvidberg Petersen, Cecilie Wennemoes Willert, Jens Velde Andersen, Mette Madsen, Helle Sonderby Waagepetersen, Niels Henning Skotte, Anne Norremolle
Summary: This study reveals that synaptic mitochondria in the striatum are more severely affected by Huntington's disease pathology than those in the cortex, leading to increased oxygen consumption and mitochondrial proton leak of striatal synaptosomes.
JOURNAL OF HUNTINGTONS DISEASE
(2022)
Editorial Material
Neurosciences
Mark O. Cunningham
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Editorial Material
Neurosciences
Mark O. Cunningham
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Neurosciences
Roger D. Traub, Miles A. Whittington, Mark O. Cunningham
Summary: This study predicts the oscillatory behavior of the medial entorhinal cortex (EC) using a neural circuit model and experimentally observed intracellular potentials. The findings have implications for understanding the neural oscillations in disorders such as Alzheimer's disease and schizophrenia.
REVIEWS IN THE NEUROSCIENCES
(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)
Article
Clinical Neurology
Anderson Brito da Silva, Jane Pennifold, Ben Henley, Koustav Chatterjee, David Bateman, Roger W. Whittaker, Abhijit Joshi, Hrishikesh Kumar, Claire Nicholson, Mark R. Baker, Stuart D. Greenhill, Richard Walsh, Stefano Seri, Roland S. G. Jones, Gavin L. Woodhall, Mark O. Cunningham
Summary: For the first time, it has been shown that perampanel has potent antiepileptic action in human FCD brain slices, likely through reducing burst firing behavior. This finding may have implications for the treatment of refractory epilepsy associated with FCD in humans.
Review
Medicine, Research & Experimental
Gareth Morris, Rachel Rowell, Mark O. Cunningham
Summary: Advancement in understanding and treating epilepsy has relied heavily on the use of animal models, but an emerging trend is to study human epileptic tissue removed during surgery. This approach offers unique insights into refractory epilepsy mechanisms and the efficacy of novel treatments.
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2021)