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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Astrocyte-to-neuron H2O2 signalling supports long-term memory formation in Drosophila and is impaired in an Alzheimer’s disease model

Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Abstract Astrocytes help protect neurons from potential damage caused by reactive oxygen species (ROS). While ROS can also exert beneficial effects, it remains unknown how neuronal signalling is activated during memory formation, and whether astrocytes play a role in this process. Here we discover an astrocyte-to-neuron H 2 O cascade Drosophila that essential for long-term formation. Stimulation of acetylcholine induces increase intracellular calcium ions, which triggers the generation extracellular superoxide (O • – ) astrocytic NADPH oxidase. Astrocyte-secreted dismutase 3 (Sod3) converts to hydrogen peroxide (H ), imported into olfactory centre, mushroom body, as revealed vivo imaging. Notably, Sod3 activity requires copper are supplied amyloid precursor protein. We find human amyloid-β peptide, implicated Alzheimer’s disease, inhibits nAChRα7 cholinergic receptor impairs formation preventing synthesis. These findings may have important implications understanding aetiology disease.

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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Neurochemical Organization of the Drosophila Brain Visualized by Endogenously Tagged Neurotransmitter Receptors

Cell Reports, Journal Year: 2020, Volume and Issue: 30(1), P. 284 - 297.e5

Published: Jan. 1, 2020

Neurotransmitters often have multiple receptors that induce distinct responses in receiving cells. Expression and localization of neurotransmitter individual neurons are therefore critical for understanding the operation neural circuits. Here we describe a comprehensive library reporter strains which convertible T2A-GAL4 cassette is inserted into endogenous receptor genes Drosophila. Using this library, profile expression 75 brain. Cluster analysis reveals neurochemical segmentation brain, distinguishing higher brain centers from rest. By recombinase-mediated exchange, convert split-GFP Tango to visualize subcellular activation dopamine specific cell types. This striking differences their localization, may underlie cellular different behavioral contexts. Our resources thus provide versatile toolkit dissecting organization function systems fly

Language: Английский

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The number of neurons in Drosophila and mosquito brains

PLoS ONE, Journal Year: 2021, Volume and Issue: 16(5), P. e0250381 - e0250381

Published: May 14, 2021

Various insect species serve as valuable model systems for investigating the cellular and molecular mechanisms by which a brain controls sophisticated behaviors. In particular, nervous system of Drosophila melanogaster has been extensively studied, yet experiments aimed at determining number neurons in are surprisingly lacking. Using isotropic fractionator coupled with immunohistochemistry, we counted total neuronal non-neuronal cells whole brain, central optic lobe . For comparison, also populations three divergent mosquito species: Aedes aegypti , Anopheles coluzzii Culex quinquefasciatus The average adult was determined to be 199,380 ±3,400 D 217,910 ±6,180 Ae 223,020 ± 4,650 An 225,911±7,220 C mean cell count vs. lobes (101,140 ±3,650 107,270 2,720), (109,140 3,550 112,000 4,280), (105,130 3,670 107,140 3,090), (108,530 ±7,990 110,670 3,950) estimated. Each comprised 89% 2% out its population. Isotropic fractionation analyses did not identify obvious sexual dimorphism population these insects. Our study provides experimental evidence brains.

Language: Английский

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Neuron–glia interaction in the Drosophila nervous system

Developmental Neurobiology, Journal Year: 2020, Volume and Issue: 81(5), P. 438 - 452

Published: Feb. 25, 2020

Abstract Animals are able to move and react in manifold ways external stimuli. Thus, environmental stimuli need be detected, information must processed, and, finally, an output decision transmitted the musculature get animal moving. All these processes depend on nervous system which comprises intricate neuronal network many glial cells. Glial cells have equally important contribution function as their counterpart. Manifold roles attributed glia ranging from controlling cell number axonal pathfinding regulation of synapse formation, function, plasticity. metabolically support neurons contribute blood–brain barrier. aforementioned aspects require extensive cell–cell interactions between Not surprisingly, found all phyla executed by evolutionarily conserved molecules. Here, we review recent advance understanding neuron–glia interaction Drosophila melanogaster suggest that work simple model organisms will shed light mammalian cells, too.

Language: Английский

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Pathogenesis of α-Synuclein in Parkinson’s Disease: From a Neuron-Glia Crosstalk Perspective

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(23), P. 14753 - 14753

Published: Nov. 25, 2022

Parkinson's disease (PD) is a progressive neurodegenerative disorder. The classical behavioral defects of PD patients involve motor symptoms such as bradykinesia, tremor, and rigidity, well non-motor anosmia, depression, cognitive impairment. Pathologically, the loss dopaminergic (DA) neurons in substantia nigra (SN) accumulation α-synuclein (α-syn)-composed Lewy bodies (LBs) neurites (LNs) are key hallmarks. Glia more than mere bystanders that simply support neurons, they actively contribute to almost every aspect neuronal development function; glial dysregulation has been implicated series diseases including PD. Importantly, amounting evidence added activation neuroinflammation new features onset progression. Thus, gaining better understanding glia, especially neuron-glia crosstalk, will not only provide insight into brain physiology events but also advance our knowledge pathologies. This review addresses current α-syn pathogenesis PD, with focus on crosstalk. Particularly, transmission between α-syn-induced activation, feedbacks DA neuron degeneration thoroughly discussed. In addition, aggregation, iron deposition, regulating ferroptosis covered. Lastly, we summarize preclinical clinical therapies, targeting treatments.

Language: Английский

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Very-long-chain fatty acids induce glial-derived sphingosine-1-phosphate synthesis, secretion, and neuroinflammation

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(5), P. 855 - 874.e5

Published: April 20, 2023

Language: Английский

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Glycolysis-derived alanine from glia fuels neuronal mitochondria for memory in Drosophila

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(11), P. 2002 - 2019

Published: Nov. 6, 2023

Abstract Glucose is the primary source of energy for brain; however, it remains controversial whether, upon neuronal activation, glucose primarily used by neurons ATP production or if partially oxidized in astrocytes, as proposed astrocyte–neuron lactate shuttle model glutamatergic neurons. Thus, an vivo picture metabolism during cognitive processes missing. Here, we uncover Drosophila melanogaster a glia-to-neuron alanine transfer involving aminotransferase that sustains memory formation. Following associative conditioning, glycolysis glial cells produces alanine, which back-converted into pyruvate cholinergic olfactory center to uphold their increased mitochondrial needs. Alanine, mediator glia–neuron coupling, could be alternative systems. In parallel, dedicated transporter imports specifically long-term memory, directly transferring use pentose phosphate pathway. Our results demonstrate compartmentalization between and

Language: Английский

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Endogenous retroviruses and TDP-43 proteinopathy form a sustaining feedback driving intercellular spread of Drosophila neurodegeneration

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 21, 2023

Inter-cellular movement of "prion-like" proteins is thought to explain propagation neurodegeneration between cells. For example, abnormally phosphorylated cytoplasmic inclusions TAR-DNA-Binding protein (TDP-43) proposed underlie progression amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). But unlike transmissible prion diseases, ALS FTD are not infectious injection aggregated TDP-43 sufficient cause disease. This suggests a missing component positive feedback necessary sustain disease progression. We demonstrate that endogenous retrovirus (ERV) expression proteinopathy mutually reinforcing. Expression either Drosophila mdg4-ERV (gypsy) or the human ERV, HERV-K (HML-2) each stimulate aggregation TDP-43. Viral ERV transmission also triggers pathology in recipient cells express physiological levels TDP-43, whether they contact at distance. mechanism potentially underlies proteinopathy-caused neurodegenerative through neuronal tissue.

Language: Английский

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