Oligodendrocytes Provide Antioxidant Defense Function for Neurons by Secreting Ferritin Heavy Chain

Cell Metabolism, Journal Year: 2020, Volume and Issue: 32(2), P. 259 - 272.e10

Published: June 11, 2020

Language: Английский

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Oxidative Metabolism Drives Immortalization of Neural Stem Cells during Tumorigenesis

Cell, Journal Year: 2020, Volume and Issue: 182(6), P. 1490 - 1507.e19

Published: Sept. 1, 2020

Language: Английский

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Glia fuel neurons with locally synthesized ketone bodies to sustain memory under starvation

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(2), P. 213 - 224

Published: Feb. 17, 2022

Abstract During starvation, mammalian brains can adapt their metabolism, switching from glucose to alternative peripheral fuel sources. In the Drosophila starved brain, memory formation is subject adaptative plasticity, but whether this adaptive plasticity relies on metabolic adaptation remains unclear. Here we show that during neurons of fly olfactory centre import and use ketone bodies (KBs) as an energy substrate sustain aversive formation. We identify local providers within cortex glia, own lipid store synthesize KBs before exporting them via monocarboxylate transporters. Finally, master sensor AMP-activated protein kinase regulates both mobilization KB export in glia. Our data provide a general schema interactions brain support when scarce.

Language: Английский

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Lipid metabolism and storage in neuroglia: role in brain development and neurodegenerative diseases

Cell & Bioscience, Journal Year: 2022, Volume and Issue: 12(1)

Published: July 12, 2022

The importance of neuroglia in maintaining normal brain function under physiological and pathological conditions has been supported by growing evidence recent years. most important issues regarding glial metabolism include the cooperation between populations neurons, morphological functional changes states, role onset progression neurodegenerative diseases. Although lipid accumulation further droplet production disease models have observed for a long time, dynamic development research years suggests its diseases was previously underestimated. First recognized as organelles storage, droplets (LDs) emerged an organelle metabolic diseases, inflammation, host defense. Dynamic within neurons cells resulting formation are present various yet their remains largely unexplored. This paper first reviews several major lipids discusses regulation different types cells. We explore potential intracellular pathogenesis neurodegeneration, starting from LDs biogenesis cells, discuss factors that promote formation, mainly focusing on oxidative stress, energy cell-neuron coupling, which closely related to etiology Finally, directions challenges neurodegeneration discussed.

Language: Английский

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Oligodendrocytes: Myelination, Plasticity, and Axonal Support

Cold Spring Harbor Perspectives in Biology, Journal Year: 2024, Volume and Issue: 16(10), P. a041359 - a041359

Published: April 15, 2024

Mikael Simons1,2, Erin M. Gibson3 and Klaus-Armin Nave4 1Institute of Neuronal Cell Biology, Technical University Munich, Munich 80802, Germany 2German Center for Neurodegenerative Diseases, Cluster Systems Neurology (SyNergy), Institute Stroke Dementia Research, 81377, 3Department Psychiatry Behavioral Sciences, Stanford School Medicine, 94305, California, USA 4Department Neurogenetics, Max Planck Multidisciplinary Göttingen 37075, Correspondence: mikael.simons{at}dzne.de; egibson1{at}stanford.edu; nave{at}mpinat.mpg.de

Language: Английский

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Regulation of Carbohydrate Energy Metabolism in Drosophila melanogaster.

PubMed, Journal Year: 2017, Volume and Issue: 207(4), P. 1231 - 1253

Published: Dec. 1, 2017

Carbohydrate metabolism is essential for cellular energy balance as well the biosynthesis of new building blocks. As animal nutrient intake displays temporal fluctuations and each cell type within possesses specific metabolic needs, elaborate regulatory systems are needed to coordinate carbohydrate in time space. regulated locally through gene networks signaling pathways, which receive inputs from sensors other such developmental signals. Superimposed on cell-intrinsic control, hormonal mediates intertissue information maintain organismal homeostasis. Misregulation causative many human diseases, diabetes cancer. Recent work Drosophila melanogaster has uncovered regulators introduced novel physiological roles previously known pathways. Moreover, genetically tractable models study metabolism-related diseases have provided insight into mechanisms pathogenesis. Due high degree conservation relevant vast possibilities analysis gene-nutrient interactions tissue-specific function, emerging an important model system research metabolism.

Language: Английский

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Drosophila glia: Few cell types and many conserved functions

Glia, Journal Year: 2018, Volume and Issue: 67(1), P. 5 - 26

Published: Nov. 15, 2018

Abstract Glial cells constitute without any dispute an essential element in providing efficiently operating nervous system. Work many labs over the last decades has demonstrated that neuronal function, from action potential generation to its propagation, eliciting synaptic responses subsequent postsynaptic integration, is evolutionarily highly conserved. Likewise, biology of glial appears conserved core elements and therefore, a deeper understanding expected benefit analyzing model organisms such as Drosophila melanogaster . particularly well suited for studying since fly system only limited number exists, which can be individually identified based on position set molecular markers. In combination with well‐known genetic tool box unprecedented level analysis feasible, not help identify novel molecules principles governing cell function but also will better understand functions first mammalian Here we review current knowledge glia spark interest using this analyze complex traits future.

Language: Английский

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Metabolic Dysfunction in Parkinson’s Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism

Brain Research Bulletin, Journal Year: 2017, Volume and Issue: 133, P. 12 - 30

Published: March 21, 2017

Language: Английский

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CrossTalk proposal: an important astrocyte‐to‐neuron lactate shuttle couples neuronal activity to glucose utilisation in the brain

The Journal of Physiology, Journal Year: 2018, Volume and Issue: 596(3), P. 347 - 350

Published: Jan. 2, 2018

We will argue here that there is net lactate transfer from astrocytes to neurons and this important for brain function. Following CrossTalk guidelines, we focus on data published over the last decade. The astrocyte-to-neuron shuttle (ANLS) hypothesis was proposed based glutamate experiments with cultured cells (Pellerin & Magistretti, 1994). Later on, comparative NMR spectroscopy confirmed are more glycolytic than (Bouzier-Sore et al. 2006), a metabolic divergence has later been explained by constitutive inhibition of phosphofructokinase in but not astrocytes, which diverts neuronal glucose flux towards pentose phosphate pathway (Herrero-Mendez 2009). Since then, other signals have found be capable, like glutamate, commanding production and/or release specifically potassium ammonium (Bittner 2011; Choi 2012; Lerchundi 2015; Sotelo-Hitschfeld 2015). In all cases, findings culture were slices or vivo (see below). contrast, could find any reports presence physiological lactate, either at rest during electrical stimulation. But what extent representative vivo? According transcriptomic analysis adult cells, difference between described also (Zhang 2014), becomes accentuated if together even so upon induction activity (Mamczur Hasel 2017). Because made glucose, uptake informs question hand. Measured tissue slices, Bergmann glia transport metabolise fluorescent analogues, NBDGs, faster neighbouring (Barros 2009; Jakoby 2014). separate study vivo, whisker stimulation caused stronger increase NBDG accumulation somatosensory cortex (Chuquet 2010). These results line much higher cytosolic NADH/NAD+ hippocampal relative (Mongeon 2016), indicative astrocytic glycolysis, decrease after blocking monocarboxylate transporter MCT2 (Diaz-Garcia Also consumption induced stimulation, phenomenon mediated sodium/bicarbonate cotransporter NBCe1 (Ruminot Astrocytic further supported an increased fluoro-deoxyglucose (FDG) response pharmacological GLT-1 (Zimmer Glial support energy metabolism demonstrated compact white matter (Saab 2016). Activity-dependent axons leads oligodendroglial energetic spiking form lactate. As it widely accepted most metabolised ends up as CO2 glial preferential implies carbon Furthermore, direct evidence orexinergic hypothalamus shown very recently (Clasadonte A contrasting conclusion reached two studies. one them, forebrains animals injected FDG used prepare nerve terminal vesicles. radioactivity present vesicles compared concentration marker N-acetylaspartate (NAA) similar starting homogenate (Patel Taken face value, similarity would mean do consume rather extreme proposition. Without information about isotope NAA leakage degradation membrane disruption/resealing prolonged density gradient centrifugation, meaning FDG/NAA ratio does seem straightforward us. second study, analogue IR2DG800 preferentially stain (Lundgaard 2015) when administered into cerebrospinal fluid, thus bypassing efficient entry circulation via endfeet. Critically, may transported substrate because its size (molecular mass 1300 Da), larger GLUT blocker cytochalasin B 480 Da) NBDGs (342 Da). Based inhomogeneous subcellular distribution, concluded probably enters endocytosis (Kovar these technical issues, doubtful articles provide compelling against ANLS. Given choice, prefer equicaloric substitution glucose- lactate-consumption intravenous infusion (Van Hall Wyss 2011). rapid use withdrawal anaesthesia, quantified approx. 5 μm/s (Funfschilling 2012). strictly coupled oxygen neuronal, follows three studies oxidised neurons. source under normal conditions, blood low? Neural activation triggers surge detected humans rodents multiple techniques, including spectroscopy, microdialysis, enzyme-based microprobes genetically encoded sensors. For example, memory task interstitial (Newman 2011) that, assuming resting level 1 mm, estimated 10 μm/s. This means some released speed commensurate rate tissue. Our interpretation access blood-borne contain glycogen Moreover, maintain high levels intracellular dynamic reservoir can quickly mobilised demand lactate-permeable ion channel gated extracellular (Sotelo-Hitschfeld Ruminot neurons, separated possess stores, poised import they lower (Machler 2016) favouring pyruvate conversion Stimulation glycolysis inferred rise insensitive blockage, interpreted ANLS However, same reported parallel unaffected lack release. Thus, contribute activity-dependent surge, only come cells. Worthy note remained peak their 2016; Diaz-Garcia 2017), conspires reversal pre-stimulation likely become reduced activity, judged pools transporters (MCTs), redundant no intercellular transfer. However several perturbation function viability genetic disruption MCTs oligodendrocytes Suzuki Funfschilling Lee Mazuel Significantly, deletion rescued maintaining requires vein, resulted deficits exogenous Even dramatic effects mitochondrial respiration mice, lethal innocuous Supplie enzymes fruit fly, deleterious (Volkenhoff summary, while jurors still out, opinion fresh numerous laboratories using diverse techniques experimental models, vitro supports (Fig. 1). look forward quantitative measurement fluxes dependence states near future. Readers invited give views accompanying issue submitting brief (250 word) comment. Comments submitted 6 weeks publication article, point discussion close authors submit 'LastWord'. Please email your comment, title declaration interest, [email protected]. moderated comments online 'supporting information' original debate once closed. L. Felipe Barros qualified Medical Doctor 1988 obtained his PhD Sciences 1993 Universidad de Chile, advised David Yudilevich. From 1996 he Wellcome Trust Fellow Steve Baldwin's lab Leeds, UK. became Assistant Professor then Associate University Chile. 2000, joined Centro Estudios Científicos Principal Investigator. How organisms manage balance energy? To address question, team developing new molecular tools, capable measuring parameters spatiotemporal resolution. Bruno Weber studied Neuroscience Zurich, Switzerland. He postdoctoral fellow Max Planck Institute Tübingen, Germany now professor Pharmacology Toxicology Zurich. His group uses wide range imaging tools cell-to-cell communication pathways involved processing cerebral cortex. working dissecting interaction vascular system, responsible adequate delivery substrates brain. well studying systems, development systems research additional group. Disclaimer: Supporting peer-reviewed copyedited. note: publisher content functionality supporting supplied authors. Any queries (other missing content) should directed corresponding author article. None declared. Both contributed conception design work, acquisition drafting work revising critically intellectual content. approved final version manuscript agree accountable aspects work. All persons designated qualify authorship, those who authorship listed. L.F.B. funded Fondecyt Grant 1160317 Chilean Government through Centers Excellence Basal Financing Program CONICYT PB-01 granted (CECs). B.W. Swiss National Science Foundation, European Community Horizon 2020 GLINT project. member Molecular Imaging Network thank members labs helpful discussions, Karen Everett critical reading manuscript.

Language: Английский

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Astrocytes, Microglia, and Parkinson’s Disease

Experimental Neurobiology, Journal Year: 2018, Volume and Issue: 27(2), P. 77 - 87

Published: April 30, 2018

Astrocytes and microglia support well-being well-function of the brain through diverse functions in both intact injured brain. For example, astrocytes maintain homeostasis microenvironment up-taking ions neurotransmitters, provide growth factors metabolites for neurons, etc. Microglia keep surveying surroundings, remove abnormal synapses or respond to injury by isolating sites expressing inflammatory cytokines. Therefore, their loss and/or functional alteration may be directly linked diseases. Since Parkinson's disease (PD)-related genes are expressed microglia, mutations these alter cells, thereby contributing onset progression. Here, we review roles brain, discuss how PD regulate functions.

Language: Английский

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