Article
Neurosciences
Fuyuko Takata-Tsuji, Naura Chounlamountri, Le-Duy Do, Camille Philippot, Julia Novion Ducassou, Yohann Coute, Sarrah Ben Achour, Jerome Honnorat, Christophe Place, Olivier Pascual
Summary: Vesicular release plays a crucial role in neurotransmission, with neurons releasing neurotransmitters rapidly and synchronously, while astrocytes modulate neurotransmission through the slower release of various transmitters. Microglia regulate astrocytic gliotransmission by influencing SNARE proteins, impacting the kinetics and overall release of gliotransmitters by astrocytes. This interaction between microglia and astrocytes may have implications for central nervous system diseases involving microglial activation.
Article
Biochemistry & Molecular Biology
Lavanya B. Achanta, Donald S. Thomas, Gary D. Housley, Caroline D. Rae
Summary: AMP-activated protein kinase (AMPK) plays an important role in balancing anabolic and catabolic activities, and may have significant impacts on brain metabolism due to its high energy demands. Through NMR spectroscopy, we activated AMPK in guinea pig cortical tissue slices using direct and indirect activators, and found that different activator concentrations had distinct effects on metabolism. Direct activation with PF 06409577 increased Krebs cycle activity and restored pyruvate metabolism, while A769662 increased lactate and alanine production, as well as labeling of citrate and glutamine. These findings highlight the complex metabolic response to AMPK activators in the brain and emphasize the need for further research on their concentration- and mechanism-dependent impact.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Cell Biology
Lauren H. Fairley, Amandine Grimm, Anne Eckert
Summary: Intercellular mitochondria transfer is a novel form of cell signalling that plays an important role in brain disorders and is considered a potential therapeutic strategy.
Article
Biochemistry & Molecular Biology
Mengmeng Jin, Hui Zhang, Baijie Xu, Yanan Li, Huiwen Qin, Shuguang Yu, Jie He
Summary: This study reveals the interaction between neurons and glial cells mediated by Jag2b and Notch3/Notch1b in the developing zebrafish retina, which is crucial for the generation and differentiation of Muller glia (MG) and the irreversible differentiation of MG.
Article
Neurosciences
Chitra Mohinder Singh Singal, Paritosh Jaiswal, Anuradha Mehta, Kanza Saleem, Pankaj Seth
Summary: The study demonstrates that HIV-1 transactivator of transcription (Tat) B increases ephrinA3 expression, decreases EAAT1 and EAAT2 expression, leading to neuronal death, while knocking down ephrinA3 can reverse this neurotoxic effect.
Review
Biochemistry & Molecular Biology
Shuanglong Yi, Linfang Wang, Honglei Wang, Margaret S. Ho, Shiping Zhang
Summary: Parkinson's disease is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of alpha-synuclein. Glial activation and neuroinflammation have been identified as new features of PD, and understanding the interaction between neurons and glia can provide insight into PD pathologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Behavioral Sciences
Catarina Carvalhas-Almeida, Joana Serra, Joaquim Moita, Claudia Cavadas, Ana Rita Alvaro
Summary: According to the World Health Organization, insomnia symptoms affect about one-third of the population, with chronic insomnia affecting around 10-15% of individuals. Chronic sleep deprivation and insomnia can lead to disruption in the internal synchronisation of biological clocks, resulting in negative health impacts. Glial cells, particularly microglia and astrocytes, play a role in circadian rhythm regulation and sleep/circadian regulation and overall healthy brain function. Understanding the interplay between glial cells and neurons is crucial in addressing sleep disorders and maintaining brain health.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Editorial Material
Neurosciences
Kelly L. Jordan-Sciutto
Summary: Despite successful viral suppression with antiretroviral (ARV) drugs, people living with HIV still experience persistent cognitive, behavioral, and motor dysfunction, raising questions about the potential contribution of these drugs themselves. Evidence suggests that ARV drugs may have an impact on the central nervous system, highlighting the importance of minimizing ARV-induced cellular and tissue dysfunction to improve the quality of life for individuals dependent on life-long ART for viral suppression.
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
(2021)
Article
Endocrinology & Metabolism
Sean-Patrick Riechers, Jelena Mojsilovic-Petrovic, Tayler B. Belton, Ram P. Chakrabarty, Mehraveh Garjani, Valentina Medvedeva, Casey Dalton, Yvette C. Wong, Navdeep S. Chandel, Gerald Dienel, Robert G. Kalb
Summary: The study investigates the metabolism of neurons expressing familial ALS genes and finds that in rodent models of fALS, there is a rewiring of metabolism with reduced neuronal lactate production and maintained or enhanced activity of the neuronal citric acid cycle. This suggests that targeting fuel utilization adjustments in neurodegenerative diseases associated with mitochondrial dysfunction can be beneficial.
MOLECULAR METABOLISM
(2022)
Article
Neurosciences
Andrew P. Patton, Nicola J. Smyllie, Johanna E. Chesham, Michael H. Hastings
Summary: The suprachiasmatic nucleus (SCN) is the master circadian clock in mammals and is generated and transmitted by the cell-autonomous transcriptional/post-translational feedback loops (TTFLs) of neurons and astrocytes. Astrocytes play an important role in circadian timekeeping by initiating rhythms and controlling the period, but neurons determine the phase of the SCN.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Multidisciplinary Sciences
Baljit S. Khakh, Steven A. Goldman
Summary: Huntington's disease (HD) is a fatal neurodegenerative disease caused by a mutation in the huntingtin gene. Astrocytes in the striatum, a brain region affected in HD, play a role in the pathology of the disease. Dysfunctions in astrocytes contribute to cellular and metabolic abnormalities in HD, suggesting the potential for therapeutic targeting of these cells to restore normal function.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Neurosciences
Du Chen, Hankui Cheng, Siyan Liu, Umar Al-Sheikh, Yuedan Fan, Duo Duan, Wenjuan Zou, Linhui Zhu, Lijun Kang
Summary: The glial L-Type VGCC EGL-19 plays a crucial role in regulating calcium variations and behavioral outputs in C. elegans, and it also affects the morphologies of sensory neurons and glial cells.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Mathematics, Applied
Ya Wang, Liang Wang, Huawei Fan, Jun Ma, Hui Cao, Xingang Wang
Summary: Recent in vivo experiments have shown that astrocytes, a type of glial cell previously thought to provide structural and metabolic support to neurons, actively participate in brain functions by regulating neural firing activities. In this study, the authors propose a complex neuron-astrocyte network model and investigate the role of astrocytes in regulating cluster synchronization behaviors of chaotic neurons. They find that a specific set of neurons form a synchronized cluster while the remaining neurons remain desynchronized. Moreover, the cluster switches between synchronous and asynchronous states in an intermittent fashion, known as the breathing cluster phenomenon. The authors conduct theoretical investigations on the synchronizability of the cluster and reveal that the cluster contents are determined by network symmetry, while the breathing of the cluster is attributed to the interplay between the neural network and the astrocyte.
Review
Medicine, Research & Experimental
Ben Rombaut, Sofie Kessels, Melissa Schepers, Assia Tiane, Dean Paes, Yevgeniya Solomina, Elisabeth Piccart, Daniel van den Hove, Bert Brone, Jos Prickaerts, Tim Vanmierlo
Summary: Synapses are essential for neuronal communication in the brain, and their balance is maintained through a careful coordination between synaptogenesis and synaptic pruning. Cell-signaling pathways play a crucial role in synaptic plasticity across different brain cells, with the involvement of second messengers like cGMP and cAMP. Targeting pathways involving phosphodiesterases (PDEs) presents a potential therapeutic strategy for combating excessive synapse loss in various neuropathologies.
Article
Neurosciences
Aline Timmermann, Dario Tascio, Ronald Jabs, Anne Boehlen, Catia Domingos, Magdalena Skubal, Wenhui Huang, Frank Kirchhoff, Christian Henneberger, Andras Bilkei-Gorzo, Gerald Seifert, Christian Steinhaeuser
Summary: NG2 glia is a unique type of macroglial cells in the CNS that receive synaptic input from neurons. Dysfunction in NG2 glia has been found to improve spatial memory but has no effect on social memory. Loss of the K+ channel Kir4.1 in NG2 glia leads to enhanced synaptic depolarizations and expression of myelin basic protein in the hippocampus. Targeted deletion of the K+ channel in NG2 glia impairs long-term potentiation at CA3-CA1 synapses, which can be rescued by extracellular application of a TrkB receptor agonist. These findings highlight the importance of proper NG2 glia function in brain function and behavior.
Article
Neurosciences
Trine Lisberg Toft-Bertelsen, Brian Roland Larsen, Sofie Kjellerup Christensen, Himanshu Khandelia, Helle S. Waagepetersen, Nanna MacAulay
Summary: The compound TGN-020 is shown to be an effective selective AQP4 inhibitor with high selectivity for AQP4, but no inhibitory effect on other AQPs (AQP1-AQP9).
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
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
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)
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)
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)
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)
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)
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
Neurosciences
Christina Kjaer, Oana Palasca, Guido Barzaghi, Lasse K. Bak, Runa K. J. Durhuus, Emil Jakobsen, Louise Pedersen, Emil D. Bartels, David P. D. Woldbye, Lars H. Pinborg, Lars Juhl Jensen
Summary: The aim of this study was to identify and validate new potential drug targets in drug-resistant mTLE by analyzing differentially expressed genes. The researchers created a consensus DEG network and validated five lead targets through qPCR, immunohistochemistry, and Western blot. The findings suggest that these targets play a crucial role in drug resistance and provide new insights for the treatment of drug-resistant mTLE.
MOLECULAR NEUROBIOLOGY
(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)