Lactate in the brain: from metabolic end-product to signalling molecule

Nature reviews. Neuroscience, Journal Year: 2018, Volume and Issue: 19(4), P. 235 - 249

Published: March 8, 2018

Language: Английский

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The Glia-Neuron Lactate Shuttle and Elevated ROS Promote Lipid Synthesis in Neurons and Lipid Droplet Accumulation in Glia via APOE/D

Cell Metabolism, Journal Year: 2017, Volume and Issue: 26(5), P. 719 - 737.e6

Published: Sept. 29, 2017

Elevated reactive oxygen species (ROS) induce the formation of lipids in neurons that are transferred to glia, where they form lipid droplets (LDs). We show glial and neuronal monocarboxylate transporters (MCTs), fatty acid transport proteins (FATPs), apolipoproteins critical for LD formation. MCTs enable glia secrete absorb lactate, which is converted pyruvate acetyl-CoA neurons. Lactate metabolites provide a substrate synthesis acids, processed by FATP apolipoproteins. In presence high ROS, inhibiting lactate transfer or lowering apolipoprotein levels decreases accumulation flies primary mouse glial-neuronal cultures. human APOE can substitute fly APOE4, an Alzheimer's disease susceptibility allele, impaired promotes neurodegeneration, providing insights into mechanisms.

Language: Английский

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Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism

The Journal of Cell Biology, Journal Year: 2018, Volume and Issue: 217(7), P. 2235 - 2246

Published: May 11, 2018

The brain’s energy demands are remarkable both in their intensity and moment-to-moment dynamic range. This perspective considers the evidence for Warburg-like aerobic glycolysis during transient metabolic response of brain to acute activation, it particularly addresses cellular mechanisms that underlie this response. temporary uncoupling between oxidative phosphorylation led proposal an astrocyte-to-neuron lactate shuttle whereby stimulation, produced by increased astrocytes is taken up neurons as primary source. However, direct idea lacking, rather supports have capacity increase own stimulation; furthermore, may export than import stimulation. possible invoking resupply also discussed, particular roles feedback signaling via adenosine diphosphate feedforward calcium ions.

Language: Английский

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A Circadian Clock in the Blood-Brain Barrier Regulates Xenobiotic Efflux

Cell, Journal Year: 2018, Volume and Issue: 173(1), P. 130 - 139.e10

Published: March 1, 2018

Language: Английский

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Energy metabolism in ALS: an underappreciated opportunity?

Acta Neuropathologica, Journal Year: 2018, Volume and Issue: 135(4), P. 489 - 509

Published: March 16, 2018

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal neurodegenerative disorder that primarily affects motor neurons. Despite our increased understanding of the genetic factors contributing to ALS, no effective treatment available. A growing body evidence shows disturbances in energy metabolism ALS. Moreover, remarkable vulnerability neurons ATP depletion has become increasingly clear. Here, we review metabolic alterations present ALS patients models, discuss selective energetic stress, provide an overview tested emerging approaches treat We believe further biology can lead identification novel therapeutic targets.

Language: Английский

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Bioenergetics and redox adaptations of astrocytes to neuronal activity

Journal of Neurochemistry, Journal Year: 2016, Volume and Issue: 139(S2), P. 115 - 125

Published: March 10, 2016

Neuronal activity is a high-energy demanding process recruiting all neural cells that adapt their metabolism to sustain the energy and redox balance of neurons. During neurotransmission, synaptic cleft glutamate activates its receptors in neurons astrocytes, before being taken up by astrocytes through costly transporters. In requirement for influx likely be met glycolysis. To enable this, are constitutively glycolytic, robustly expressing 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3), an enzyme negligibly present continuous degradation because ubiquitin-proteasome pathway via anaphase-promoting complex/cyclosome (APC)-Cdh1. Additional factors contributing glycolytic frame may include 5'-AMP-activated protein kinase (AMPK), hypoxia-inducible factor-1 (HIF-1), pyruvate muscle isoform-2 (PKM2), dehydrogenase kinase-4 (PDK4), lactate dehydrogenase-B, or monocarboxylate transporter-4 (MCT4). Neurotransmission-associated messengers, such as nitric oxide ammonium, stimulate release from astrocytes. Astrocyte-derived thus sustains needs neurons, which contrast mainly rely on oxidative phosphorylation. unavoidably triggers reactive oxygen species, but antioxidant defense weak; hence, they use glucose oxidation pentose-phosphate preserve status. Furthermore, coupled with erythroid-derived 2-like 2 (Nrf2) mediated transcriptional activation genes boost de novo glutathione biosynthesis neighbor Thus, bioenergetics programs adapted neuronal survival. Developing therapeutic strategies interfere these pathways useful combat neurological diseases. Our current knowledge brain's management requirements associated herein revisited. The astrocyte-neuronal shuttle (ANLS) explains neurotransmission. neurotransmission increased mitochondrial species By coupling glutamatergic genes, provide neuroprotective (ANGS). This article part 60th Anniversary special issue.

Language: Английский

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The Axon-Myelin Unit in Development and Degenerative Disease

Frontiers in Neuroscience, Journal Year: 2018, Volume and Issue: 12

Published: July 11, 2018

Axons are electrically excitable, cable-like neuronal processes that relay information between neurons within the nervous system and peripheral target tissues. In central systems, most axons over a critical diameter enwrapped by myelin, which reduces internodal membrane capacitance facilitates rapid conduction of electrical impulses. The spirally wrapped myelin sheath, is an evolutionary specialisation vertebrates, produced oligodendrocytes Schwann cells; in mammals myelination occurs during postnatal development after have established connection with their targets. Myelin covers vast majority axonal surface, influencing axon's physical shape, localisation molecules on its composition extracellular fluid (in periaxonal space) immerses it. unique architecture myelinated axon, crucial to function as conduit long distances, renders it particularly susceptible injury confers specific survival maintenance requirements. Moreover, myelinating cells play fundamental role support, at least part providing metabolic substrates underlying axon fuel energy this review we will describe normal morphology, ultrastructure axons, discuss how these change following disease, or experimental perturbation, particular focus cell plays shaping supporting axon.

Language: Английский

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Myelin dynamics: protecting and shaping neuronal functions

Current Opinion in Neurobiology, Journal Year: 2017, Volume and Issue: 47, P. 104 - 112

Published: Nov. 20, 2017

Language: Английский

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Upregulated energy metabolism in the Drosophila mushroom body is the trigger for long-term memory

Nature Communications, Journal Year: 2017, Volume and Issue: 8(1)

Published: June 5, 2017

Abstract Efficient energy use has constrained the evolution of nervous systems. However, it is unresolved whether metabolism may resultantly regulate major brain functions. Our observation that Drosophila flies double their sucrose intake at an early stage long-term memory formation initiated investigation how intervenes in this process. Cellular-resolution imaging reveals a concurrent elevation consumption neurons mushroom body, fly’s centre. Strikingly, upregulation body flux both necessary and sufficient to drive formation. This effect triggered by specific pair dopaminergic afferent bodies, via D5-like DAMB dopamine receptor. Hence, signalling mediates switch controls encoding. data thus point instructional role for execution demanding higher

Language: Английский

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A single-cell transcriptomic atlas of the adult Drosophila ventral nerve cord

eLife, Journal Year: 2020, Volume and Issue: 9

Published: April 21, 2020

The Drosophila ventral nerve cord (VNC) receives and processes descending signals from the brain to produce a variety of coordinated locomotor outputs. It also integrates sensory information periphery sends ascending brain. We used single-cell transcriptomics generate an unbiased classification cellular diversity in VNC five-day old adult flies. produced atlas 26,000 high-quality cells, representing more than 100 transcriptionally distinct cell types. predominant gene signatures defining neuronal types reflect shared developmental histories based on neuroblast which cells were derived, as well their birth order. relative position along anterior-posterior axis could be assigned using Hox expression. This transcriptional fly will valuable resource for future studies neurodevelopment behavior.

Language: Английский

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