Small is fast: astrocytic glucose and lactate metabolism at cellular resolution

Barros, L. Felipe; Martín, Alejandro San; Sotelo-Hitschfeld, Tamara; Lerchundi, Rodrigo; Fernández‐Moncada, Ignacio; Ruminot, Iván; Gutiérrez, Robin; Valdebenito, Rocío; Ceballo, Sebastián; Alegría, Karin; Baeza-Lehnert, Felipe; Espinoza, David

doi:10.3389/fncel.2013.00027

Cited by 53 publications

(44 citation statements)

References 50 publications

(70 reference statements)

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“…In particular, experiments involving awake animals may more accurately reflect brain metabolic states, as anesthetics are known to decrease metabolic rates (Alkire et al, 1995, 1997, 1999). It would also be beneficial to directly visualize in vivo glucose and lactate levels (possibly via fluorescent sensors for glucose or lactate) to determine metabolite concentrations in different cell populations in various brain regions during activation (Barros et al, 2013; San Martin et al, 2013). …”

Section: Astrocyte Lactate Fuels Neuronal Metabolismmentioning

confidence: 99%

Multifunctional role of astrocytes as gatekeepers of neuronal energy supply

Stobart¹,

Anderson²

2013

Front. Cell. Neurosci.

208

171

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Dynamic adjustments to neuronal energy supply in response to synaptic activity are critical for neuronal function. Glial cells known as astrocytes have processes that ensheath most central synapses and express G-protein-coupled neurotransmitter receptors and transporters that respond to neuronal activity. Astrocytes also release substrates for neuronal oxidative phosphorylation and have processes that terminate on the surface of brain arterioles and can influence vascular smooth muscle tone and local blood flow. Membrane receptor or transporter-mediated effects of glutamate represent a convergence point of astrocyte influence on neuronal bioenergetics. Astrocytic glutamate uptake drives glycolysis and subsequent shuttling of lactate from astrocytes to neurons for oxidative metabolism. Astrocytes also convert synaptically reclaimed glutamate to glutamine, which is returned to neurons for glutamate salvage or oxidation. Finally, astrocytes store brain energy currency in the form of glycogen, which can be mobilized to produce lactate for neuronal oxidative phosphorylation in response to glutamatergic neurotransmission. These mechanisms couple synaptically driven astrocytic responses to glutamate with release of energy substrates back to neurons to match demand with supply. In addition, astrocytes directly influence the tone of penetrating brain arterioles in response to glutamatergic neurotransmission, coordinating dynamic regulation of local blood flow. We will describe the role of astrocytes in neurometabolic and neurovascular coupling in detail and discuss, in turn, how astrocyte dysfunction may contribute to neuronal bioenergetic deficit and neurodegeneration. Understanding the role of astrocytes as a hub for neurometabolic and neurovascular coupling mechanisms is a critical underpinning for therapeutic development in a broad range of neurodegenerative disorders characterized by chronic generalized brain ischemia and brain microvascular dysfunction.

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Section: Astrocyte Lactate Fuels Neuronal Metabolismmentioning

confidence: 99%

Multifunctional role of astrocytes as gatekeepers of neuronal energy supply

Stobart¹,

Anderson²

2013

Front. Cell. Neurosci.

208

171

View full text Add to dashboard Cite

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“…Upon binding of a glucose molecule, the fusion protein undergoes a conformational change, leading to increased FRET when CFP is excited [58]. More recently, a similarly constructed FRET sensor for lactate has also been described, and used to quantitatively compare lactate flux in primary and cancerous glial cells at a single cell resolution [59,60]. …”

Section: Spatiotemporally Resolved Metabolic Analysismentioning

confidence: 99%

Towards high resolution analysis of metabolic flux in cells and tissues

Sims

Manteiga

Lee

2013

Current Opinion in Biotechnology

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Metabolism extracts chemical energy from nutrients, uses this energy to form building blocks for biosynthesis, and interconverts between various small molecules that coordinate the activities of cellular pathways. The metabolic state of a cell is increasingly recognized to determine the phenotype of not only metabolically active cell types such as liver, muscle, and adipose, but also other specialized cell types such as neurons and immune cells. This review focuses on methods to quantify intracellular reaction flux as a measure of cellular metabolic activity, with emphasis on studies involving cells of mammalian tissue. Two key areas are highlighted for future development, single cell metabolomics and noninvasive imaging, which could enable spatiotemporally resolved analysis and thereby overcome issues of heterogeneity, a distinctive feature of tissue metabolism.

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“…[6][7][8] Other non-destructive approaches include Raman spectroscopy, [9] electrochemistry, [10] and microfluidics. [30][31][32][33][34][35] Decreasing cell volumes from plants (pL to low nL range), to animals (low pL range), to microbes (low fL range) present mounting difficulties for sample manipulation, and the correspondingly diminishing amounts of biomolecules re-quire increasing sensitivities for detection and identification. [30][31][32][33][34][35] Decreasing cell volumes from plants (pL to low nL range), to animals (low pL range), to microbes (low fL range) present mounting difficulties for sample manipulation, and the correspondingly diminishing amounts of biomolecules re-quire increasing sensitivities for detection and identification.…”

Section: Introductionmentioning

confidence: 99%

Single‐Cell Mass Spectrometry Approaches to Explore Cellular Heterogeneity

2018

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Compositional diversity is a fundamental property in cell populations. Single-cell analysis promises new insight into this cellular heterogeneity on the genomic, transcriptomic, proteomic, and metabolomic levels. Mass spectrometry (MS) is a label-free technique that enables the multiplexed analysis of proteins, peptides, lipids, and metabolites in individual cells. The abundances of these molecular classes are correlated with the physiological states and environmental responses of the cells. In this Minireview, we discuss recent advances in single-cell MS techniques with an emphasis on sampling and ionization methods developed for volume-limited samples. Strategies for sample treatment, separation methods, and data analysis require special considerations for single cells. Ongoing analytical challenges include subcellular heterogeneity, non-normal statistical distributions of cellular properties, and the need for high-throughput, high molecular coverage and minimal perturbation.

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Small is fast: astrocytic glucose and lactate metabolism at cellular resolution

Cited by 53 publications

References 50 publications

Multifunctional role of astrocytes as gatekeepers of neuronal energy supply

Multifunctional role of astrocytes as gatekeepers of neuronal energy supply

Towards high resolution analysis of metabolic flux in cells and tissues

Single‐Cell Mass Spectrometry Approaches to Explore Cellular Heterogeneity

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