A perspective on astrocyte regulation of neural circuit function and animal behavior

Glia, Journal Year: 2022, Volume and Issue: 70(8), P. 1554 - 1580

Published: March 17, 2022

Studies over the past two decades have demonstrated that astrocytes are tightly associated with neurons and play pivotal roles in neural circuit development, operation, adaptation health disease. Nevertheless, precisely how integrate diverse neuronal signals, modulate structure function at multiple temporal spatial scales, influence animal behavior or disease through aberrant excitation molecular output remains unclear. This Perspective discusses new state-of-the-art approaches, including fluorescence indicators, opto- chemogenetic actuators, genetic targeting tools, quantitative behavioral assays, computational methods, might help resolve these longstanding questions. It also addresses complicating factors interpreting astrocytes' role regulation behavior, such as their heterogeneity, metabolism, inter-glial communication. Research on questions should provide a deeper mechanistic understanding of astrocyte-neuron assemblies' function, complex behaviors,

Language: Английский

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Probing organoid metabolism using fluorescence lifetime imaging microscopy (FLIM): The next frontier of drug discovery and disease understanding

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 201, P. 115081 - 115081

Published: Aug. 28, 2023

Language: Английский

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Metabolic Recruitment in Brain Tissue

Annual Review of Physiology, Journal Year: 2022, Volume and Issue: 85(1), P. 115 - 135

Published: Oct. 21, 2022

Information processing imposes urgent metabolic demands on neurons, which have negligible energy stores and restricted access to fuel. Here, we discuss recruitment, the tissue-level phenomenon whereby active neurons harvest resources from their surroundings. The primary event is neuronal release of K + that mirrors workload. Astrocytes sense in exquisite fashion thanks unique coexpression NBCe1 α2β2 Na /K ATPase, within seconds switch Crabtree metabolism, involving GLUT1, aerobic glycolysis, transient suppression mitochondrial respiration, lactate export. surge serves as a secondary recruiter by inhibiting glucose consumption distant cells. Additional recruiters are glutamate, nitric oxide, ammonium, signal over different spatiotemporal domains. net outcome these events more glucose, lactate, oxygen made available. Metabolic recruitment works alongside neurovascular coupling various averaging strategies support inordinate dynamic range individual neurons.

Language: Английский

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The Astrocyte: Metabolic Hub of the Brain

Cold Spring Harbor Perspectives in Biology, Journal Year: 2024, Volume and Issue: 16(9), P. a041355 - a041355

Published: March 4, 2024

Astrocytic metabolism has taken center stage. Interposed between the neuron and vasculature, astrocytes exert control over fluxes of energy building blocks required for neuronal activity plasticity. They are also key to local detoxification waste recycling. Whereas neurons metabolically rigid, can switch different metabolic profiles according demand nutritional state organism. Their even seems be instructive peripheral nutrient mobilization been implicated in information processing behavior. Here, we summarize recent progress our understanding astrocytic its effects on homeostasis cognition.

Language: Английский

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Gray and white matter astrocytes differ in basal metabolism but respond similarly to neuronal activity

Glia, Journal Year: 2022, Volume and Issue: 71(2), P. 229 - 244

Published: Sept. 5, 2022

Abstract Astrocytes are a heterogeneous population of glial cells in the brain, which adapt their properties to requirements local environment. Two major groups astrocytes protoplasmic residing gray matter as well fibrous white matter. Here, we compared energy metabolism cortex and corpus callosum representative regions, acute brain slices taking advantage genetically encoded fluorescent nanosensors for NADH/NAD + redox ratio ATP. presented more reduced basal ratio, lower cytosolic concentration ATP cortical astrocytes. In astrocytes, neurotransmitter glutamate increased extracellular concentrations K , typical correlates neuronal activity, induced ratio. While application decreased [ATP], combination resulted an increase levels. Strikingly, very similar regulation by was observed callosum. Finally, strong intrinsic activity provoked bicuculline withdrawal Mg 2+ caused shift state slight reduction [ATP] summary, shows distinct properties, but qualitatively responses probably reflecting different environment these regions.

Language: Английский

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Enlightening brain energy metabolism

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 184, P. 106211 - 106211

Published: June 21, 2023

Brain tissue metabolism is distributed across several cell types and subcellular compartments, which activate at different times with temporal patterns. The introduction of genetically-encoded fluorescent indicators that are imaged using time-lapse microscopy has opened the possibility studying brain cellular sub-cellular levels. There for sugars, monocarboxylates, Krebs cycle intermediates, amino acids, cofactors, energy nucleotides, inform about relative levels, concentrations fluxes. This review offers a brief survey metabolic have been validated in cells, some illustrative examples from literature. Whereas only small fraction metabolome currently accessible to probes, there grounds be optimistic coming developments application these tools study disease.

Language: Английский

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Out of the cycle: Impact of cell cycle aberrations on cancer metabolism and metastasis

International Journal of Cancer, Journal Year: 2022, Volume and Issue: 152(8), P. 1510 - 1525

Published: Sept. 12, 2022

The use of cell cycle inhibitors has necessitated a better understanding the in tumor biology to optimize therapeutic approach. Cell aberrations are common cancers, and it is increasingly acknowledged that these exert oncogenic effects beyond cycle. Multiple facets such as cancer metabolism, immunity metastasis also affected, all which effect proliferation alone. This review comprehensively summarized important recent findings advances interrelated processes. In regulators can modulate various pathways aerobic glycolysis, glucose uptake gluconeogenesis, mainly through transcriptional regulation kinase activities. Amino acid metabolism regulated progression. On metastasis, metabolic plasticity, immune evasion, microenvironment adaptation metastatic site colonization intricately related cycle, with distinct regulatory mechanisms at each step invasion dissemination. Throughout synthesis current understanding, knowledge gaps limitations literature highlighted, new approaches combinational therapy challenges tackling emerging targeted resistance. A greater how modulates diverse aspects hopefully shed light on identifying molecular targets by harnessing vast potential

Language: Английский

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Genetically Encoded Metabolic Sensors to Study Retina Metabolism

Advances in experimental medicine and biology, Journal Year: 2025, Volume and Issue: unknown, P. 465 - 469

Published: Jan. 1, 2025

Language: Английский

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De novo genome assembly of the bioluminescent mushroom Omphalotus guepiniiformis reveals an Omphalotus-specific lineage of the luciferase gene block

Genomics, Journal Year: 2022, Volume and Issue: 114(6), P. 110514 - 110514

Published: Nov. 1, 2022

Omphalotus guepiniiformis, a bioluminescent mushroom species, is source of the potentially valuable anticancer chemical. To provide genome information, we de novo assembled high-quality O. guepiniiformis using two Next-Generation sequencing techniques, PacBio and Illumina sequencing. Our draft comprises 42.5 Mbp sequence with only 80 contigs an N50 length over 1 Mbp. There were 15,554 predicted coding genes, 7693 genes functionally annotated Gene Ontology terms. We performed genomic study focusing on pathway cluster by comparing 17 luminescent 23 non-luminescent Agaricales species belonging to genera. Synteny analysis regions near inferred that lineage was genus-specific. In summary, our provides significant biological insights into this organism, including evolution luciferase gene block, forms basis for future analyses.

Language: Английский

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In vivo calibration of genetically encoded metabolite biosensors must account for metabolite metabolism during calibration and cellular volume

Journal of Neurochemistry, Journal Year: 2023, Volume and Issue: 168(5), P. 506 - 532

Published: Feb. 2, 2023

Isotopic assays of brain glucose utilization rates have been used for more than four decades to establish relationships between energetics, functional activity, and neurotransmitter cycling. Limitations these methods include the relatively long time (1-60 min) determination labeled metabolite levels lack cellular resolution. Identification quantification fuels neurons astrocytes that support activation higher functions are a major, unresolved issues. Glycolysis is preferentially up-regulated during even though oxygen level supply adequate, causing lactate concentrations quickly rise alerting, sensory processing, cognitive tasks, memory consolidation. However, fate (rapid release from or cell-cell shuttling coupled with local oxidation) disputed. Genetically encoded biosensors can determine intracellular report real-time responses sensory, behavioral, biochemical challenges at level. Kinetics courses concentration changes informative, but accurate biosensor calibration required quantitative comparisons in neurons. An vivo procedure Laconic involves depletion by intravenous pyruvate-mediated trans-acceleration efflux followed sensor saturation infusion high doses plus ammonium chloride. In present paper, validity this questioned because rapid lactate-pyruvate interconversion blood, preferential neuronal oxidation both monocarboxylates, on-going glycolytic metabolism, volumes were not taken into account. Calibration pitfalls also apply other standardized substrates be metabolized peripheral tissues. We discuss how technical shortcomings negate conclusion calibrations existence an astrocyte-neuron gradient linked fuel activity.

Language: Английский

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