МЕТАБОЛИЧЕСКАЯ ПЛАСТИЧНОСТЬ АСТРОЦИТОВ
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Ключевые слова

астроциты
нейроны
пластичность
церебральный метаболизм
нейродегенеративные заболевания

Аннотация

Астроциты являются наиболее многочисленными глиальными клетками центральной нервной системы, расположенными между микрососудистой сетью головного мозга и синапсами нейронов, тем самым опосредуя поглощение питательных веществ из системного кровотока. Кроме того, астроциты, благодаря своему уникальному анатомическому расположению, обладают высокой ферментативной способностью к гликолизу, гликогенезу и метаболизму липидов, обеспечивая нейроны необходимыми питательными веществами в качестве источника энергии, что указывает о ключевой роли астроцитов в метаболизме мозга. Следовательно, нарушение функций астроглии может привести к развитию нейродегенеративных заболеваний, при которых метаболические нарушения ускоряют повреждение нейронов. Принимая во внимание важную роль астроцитов в регуляции гомеостаза головного мозга и наличие тесной метаболической взаимосвязи с нейронами, в этом обзоре мы рассматриваем пластичность энергетического метаболизма астроцитов в физиологических условиях и ее влияние на функции мозга при развитии нейродегенеративных заболеваний. При этом понимание механизма, лежащего в основе метаболической пластичности астроцитов, даст возможность определить новые потенциальные диагностические биомаркеры и терапевтические мишени для коррекции нейродегенерации и возрастных дисфункций головного мозга.

https://doi.org/10.31857/S0044452921060036
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Литература

Jakovcevic D, Harder DR (2007) Role of astrocytes in matching blood flow to neuronal activity. Curr Top Dev Biol 79:75–97. https://doi.org/10.1016/S0070-2153(06)79004-4

Marina N, Christie IN, Korsak A, Doronin M, Brazhe A, Hosford PS, Wells JA, Sheikhbahaei S, Humoud I, Paton JFR, Lythgoe MF, Semyanov A, Kasparov S, Gourine AV (2020) Astrocytes monitor cerebral perfusion and control systemic circulation to maintain brain blood flow. Nat Commun 11:131. https://doi.org/10.1038/s41467-019-13956-y

Kim KJ, Iddings JA, Stern JE, Blanco VM, Croom D, Kirov SA, Filosa JA (2015) Astrocyte Contributions to Flow/Pressure-Evoked Parenchymal Arteriole Vasoconstriction. J Neurosci 35:8245–8257. https://doi.org/10.1523/JNEUROSCI.4486-14.2015

Magistretti PJ (2011) Neuron-glia metabolic coupling and plasticity. Exp Physiol 96:407–410. https://doi.org/10.1113/expphysiol.2010.053157

Ioannou MS, Jackson J, Sheu S-H, Chang C-L, Weigel AV, Liu H, Pasolli HA, Xu CS, Pang S, Matthies D, Hess HF, Lippincott-Schwartz J, Liu Z (2019) Neuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid Toxicity. Cell 177:1522–1535.e14. https://doi.org/10.1016/j.cell.2019.04.001

(2009) The role of astroglia in neuroprotection. Dialogues Clin Neurosci 11:281–295. https://doi.org/10.31887/DCNS.2009.11.3/mbelanger

Paixão S, Klein R (2010) Neuron–astrocyte communication and synaptic plasticity. Current Opin Neurobiol 20:466–473. https://doi.org/10.1016/j.conb.2010.04.008

Papouin T, Dunphy J, Tolman M, Foley JC, Haydon PG (2017) Astrocytic control of synaptic function. Phil Trans R Soc B 372:20160154. https://doi.org/10.1098/rstb.2016.0154

Vaidyanathan TV, Collard M, Yokoyama S, Reitman ME, Poskanzer KE (2021) Cortical astrocytes independently regulate sleep depth and duration via separate GPCR pathways. eLife 10:e63329. https://doi.org/10.7554/eLife.63329

Santello M, Toni N, Volterra A (2019) Astrocyte function from information processing to cognition and cognitive impairment. Nat Neurosci 22:154–166. https://doi.org/10.1038/s41593-018-0325-8

Gourine AV, Kasymov V, Marina N, Tang F, Figueiredo MF, Lane S, Teschemacher AG, Spyer KM, Deisseroth K, Kasparov S (2010) Astrocytes Control Breathing Through pH-Dependent Release of ATP. Science 329:571–575. https://doi.org/10.1126/science.1190721

Pfrieger FW, Ungerer N (2011) Cholesterol metabolism in neurons and astrocytes. Progr Lipid Res 50:357–371. https://doi.org/10.1016/j.plipres.2011.06.002

García-Krauss A, Ferrada L, Astuya A, Salazar K, Cisternas P, Martínez F, Ramírez E, Nualart F (2016) Dehydroascorbic Acid Promotes Cell Death in Neurons Under Oxidative Stress: a Protective Role for Astrocytes. Mol Neurobiol 53:5847–5863. https://doi.org/10.1007/s12035-015-9497-3

Velasco‐Estevez M, Rolle SO, Mampay M, Dev KK, Sheridan GK (2020) Piezo1 regulates calcium oscillations and cytokine release from astrocytes. Glia 68:145–160. https://doi.org/10.1002/glia.23709

Mahan V (2019) Neurointegrity and europhysiology: astrocyte, glutamate, and carbon monoxide interactions. Med Gas Res 9:0. https://doi.org/10.4103/2045-9912.254639

Alberini CM, Cruz E, Descalzi G, Bessières B, Gao V (2018) Astrocyte glycogen and lactate: New insights into learning and memory mechanisms. Glia 66:1244–1262. https://doi.org/10.1002/glia.23250

Bali P, Banik A, Nehru B, Anand A (2019) Neurotrophic Factors Mediated Activation of Astrocytes Ameliorate Memory Loss by Amyloid Clearance after Transplantation of Lineage Negative Stem Cells. Mol Neurobiol 56:8420–8434. https://doi.org/10.1007/s12035-019-01680-z

Christopherson KS, Ullian EM, Stokes CCA, Mullowney CE, Hell JW, Agah A, Lawler J, Mosher DF, Bornstein P, Barres BA (2005) Thrombospondins Are Astrocyte-Secreted Proteins that Promote CNS Synaptogenesis. Cell 120:421–433. https://doi.org/10.1016/j.cell.2004.12.020

Bayraktar OA, Fuentealba LC, Alvarez-Buylla A, Rowitch DH (2015) Astrocyte Development and Heterogeneity. Cold Spring Harb Perspect Biol 7:a020362. https://doi.org/10.1101/cshperspect.a020362

Zhou B, Zuo Y, Jiang R (2019) Astrocyte morphology: Diversity, plasticity, and role in neurological diseases. CNS Neurosci Ther 25:665–673. https://doi.org/10.1111/cns.13123

Waterson MJ, Horvath TL (2015) Neuronal Regulation of Energy Homeostasis: Beyond the Hypothalamus and Feeding. Cell Metabolism 22:962–970. https://doi.org/10.1016/j.cmet.2015.09.026

Herculano-Houzel S (2011) Scaling of Brain Metabolism with a Fixed Energy Budget per Neuron: Implications for Neuronal Activity, Plasticity and Evolution. PLoS ONE 6:e17514. https://doi.org/10.1371/journal.pone.0017514

Arluison M, Quignon M, Nguyen P, Thorens B, Leloup C, Penicaud L (2004) Distribution and anatomical localization of the glucose transporter 2 (GLUT2) in the adult rat brain—an immunohistochemical study. J Chem Neuroanat 28:117–136. https://doi.org/10.1016/j.jchemneu.2004.05.009

Moreira TJ, Pierre K, Maekawa F, Repond C, Cebere A, Liljequist S, Pellerin L (2009) Enhanced Cerebral Expression of MCT1 and MCT2 in a Rat Ischemia Model Occurs in Activated Microglial Cells. J Cereb Blood Flow Metab 29:1273–1283. https://doi.org/10.1038/jcbfm.2009.50

Coraci IS, Husemann J, Berman JW, Hulette C, Dufour JH, Campanella GK, Luster AD, Silverstein SC, El Khoury JB (2002) CD36, a Class B Scavenger Receptor, Is Expressed on Microglia in Alzheimer’s Disease Brains and Can Mediate Production of Reactive Oxygen Species in Response to β-Amyloid Fibrils. Am J Pathol 160:101–112. https://doi.org/10.1016/S0002-9440(10)64354-4

Bélanger M, Allaman I, Magistretti PJ (2011) Brain Energy Metabolism: Focus on Astrocyte-Neuron Metabolic Cooperation. Cell Metabolism 14:724–738. https://doi.org/10.1016/j.cmet.2011.08.016

Mathiisen TM, Lehre KP, Danbolt NC, Ottersen OP (2010) The perivascular astroglial sheath provides a complete covering of the brain microvessels: An electron microscopic 3D reconstruction. Glia 58:1094–1103. https://doi.org/10.1002/glia.20990

Dienel GA (2019) Brain Glucose Metabolism: Integration of Energetics with Function. Physiol Rev 99:949–1045. https://doi.org/10.1152/physrev.00062.2017

Sonnay S, Poirot J, Just N, Clerc A-C, Gruetter R, Rainer G, Duarte JMN (2018) Astrocytic and neuronal oxidative metabolism are coupled to the rate of glutamate-glutamine cycle in the tree shrew visual cortex. Glia 66:477–491. https://doi.org/10.1002/glia.23259

Kubotera H, Ikeshima-Kataoka H, Hatashita Y, Allegra Mascaro AL, Pavone FS, Inoue T (2019) Astrocytic endfeet re-cover blood vessels after removal by laser ablation. Sci Rep 9:1263. https://doi.org/10.1038/s41598-018-37419-4

Pascual O, Ben Achour S, Rostaing P, Triller A, Bessis A (2012) Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission. Proc Natl Acad Sci U S A 109:E197–E205. https://doi.org/10.1073/pnas.1111098109

Chen S-H, Oyarzabal EA, Sung Y-F, Chu C-H, Wang Q, Chen S-L, Lu R-B, Hong J-S (2015) Microglial regulation of immunological and neuroprotective functions of astroglia: Microglia Regulate Astroglia in Inflammation. Glia 63:118–131. https://doi.org/10.1002/glia.22738

Anderson KM, Collins MA, Kong R, Fang K, Li J, He T, Chekroud AM, Yeo BTT, Holmes AJ (2020) Convergent molecular, cellular, and cortical neuroimaging signatures of major depressive disorder. Proc Natl Acad Sci U S A 117:25138–25149. https://doi.org/10.1073/pnas.2008004117

di Domenico A, Carola G, Calatayud C, Pons-Espinal M, Muñoz JP, Richaud-Patin Y, Fernandez-Carasa I, Gut M, Faella A, Parameswaran J, Soriano J, Ferrer I, Tolosa E, Zorzano A, Cuervo AM, Raya A, Consiglio A (2019) Patient-Specific iPSC-Derived Astrocytes Contribute to Non-Cell-Autonomous Neurodegeneration in Parkinson’s Disease. Stem Cell Rep 12:213–229. https://doi.org/10.1016/j.stemcr.2018.12.011

Chung W-S, Verghese PB, Chakraborty C, Joung J, Hyman BT, Ulrich JD, Holtzman DM, Barres BA (2016) Novel allele-dependent role for APOE in controlling the rate of synapse pruning by astrocytes. Proc Natl Acad Sci U S A 113:10186–10191. https://doi.org/10.1073/pnas.1609896113

Gurven M, Walker R (2006) Energetic demand of multiple dependents and the evolution of slow human growth. Proc R Soc B 273:835–841. https://doi.org/10.1098/rspb.2005.3380

Bock J, Sellen DW (2002) Childhood and the evolution of the human life course: An introduction. Hum Nat 13:153–159. https://doi.org/10.1007/s12110-002-1006-5

Navarrete A, van Schaik CP, Isler K (2011) Energetics and the evolution of human brain size. Nature 480:91–93. https://doi.org/10.1038/nature10629

Schuppli C, Isler K, van Schaik CP (2012) How to explain the unusually late age at skill competence among humans. J Human Evolut 63:843–850. https://doi.org/10.1016/j.jhevol.2012.08.009

Kuzawa CW, Chugani HT, Grossman LI, Lipovich L, Muzik O, Hof PR, Wildman DE, Sherwood CC, Leonard WR, Lange N (2014) Metabolic costs and evolutionary implications of human brain development. Proc Natl Acad Sci U S A 111:13010–13015. https://doi.org/10.1073/pnas.1323099111

Pontzer H, Brown MH, Raichlen DA, Dunsworth H, Hare B, Walker K, Luke A, Dugas LR, Durazo-Arvizu R, Schoeller D, Plange-Rhule J, Bovet P, Forrester TE, Lambert EV, Thompson ME, Shumaker RW, Ross SR (2016) Metabolic acceleration and the evolution of human brain size and life history. Nature 533:390–392. https://doi.org/10.1038/nature17654

Namba T, Dóczi J, Pinson A, Xing L, Kalebic N, Wilsch-Bräuninger M, Long KR, Vaid S, Lauer J, Bogdanova A, Borgonovo B, Shevchenko A, Keller P, Drechsel D, Kurzchalia T, Wimberger P, Chinopoulos C, Huttner WB (2020) Human-Specific ARHGAP11B Acts in Mitochondria to Expand Neocortical Progenitors by Glutaminolysis. Neuron 105:867–881.e9. https://doi.org/10.1016/j.neuron.2019.11.027

Zintel TM, Pizzollo J, Claypool CG, Babbitt CC (2020) Astrocytes drive divergent metabolic gene expression in humans and chimpanzees. Evolut Biol. https://doi.org/10.1101/2020.11.09.374835

Verkhratsky A, Nedergaard M (2016) The homeostatic astroglia emerges from evolutionary specialization of neural cells. Phil Trans R Soc B 371:20150428. https://doi.org/10.1098/rstb.2015.0428

Dienel GA, Rothman DL (2019) Glycogenolysis in Cerebral Cortex During Sensory Stimulation, Acute Hypoglycemia, and Exercise: Impact on Astrocytic Energetics, Aerobic Glycolysis, and Astrocyte-Neuron Interactions. In: DiNuzzo M, Schousboe A (eds) Brain Glycogen Metabolism. Springer Int Publ, Cham 209–267.

Falkowska A, Gutowska I, Goschorska M, Nowacki P, Chlubek D, Baranowska-Bosiacka I (2015) Energy Metabolism of the Brain, Including the Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism. IJMS 16:25959–25981. https://doi.org/10.3390/ijms161125939

Li B, Freeman RD (2015) Neurometabolic coupling between neural activity, glucose, and lactate in activated visual cortex. J Neurochem 135:742–754. https://doi.org/10.1111/jnc.13143

Goyal MS, Hawrylycz M, Miller JA, Snyder AZ, Raichle ME (2014) Aerobic Glycolysis in the Human Brain Is Associated with Development and Neotenous Gene Expression. Cell Metabolism 19:49–57. https://doi.org/10.1016/j.cmet.2013.11.020

Almeida A, Moncada S, Bolaños JP (2004) Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructo-2-kinase pathway. Nat Cell Biol 6:45–51. https://doi.org/10.1038/ncb1080

Allaman I, Pellerin L, Magistretti PJ (2000) Protein targeting to glycogen mRNA expression is stimulated by noradrenaline in mouse cortical astrocytes. Glia 30:382–391.

Drulis-Fajdasz D, Gizak A, Wójtowicz T, Wiśniewski JR, Rakus D (2018) Aging-associated changes in hippocampal glycogen metabolism in mice. Evidence for and against astrocyte-to-neuron lactate shuttle. Glia 66:1481–1495. https://doi.org/10.1002/glia.23319

Gómez-Gonzalo M, Martin-Fernandez M, Martínez-Murillo R, Mederos S, Hernández-Vivanco A, Jamison S, Fernandez AP, Serrano J, Calero P, Futch HS, Corpas R, Sanfeliu C, Perea G, Araque A (2017) Neuron-astrocyte signaling is preserved in the aging brain: Neuron-Astrocyte Signaling in Aging Brain. Glia 65:569–580. https://doi.org/10.1002/glia.23112

Yellen G (2018) Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism. J Cell Biol 217:2235–2246. https://doi.org/10.1083/jcb.201803152

Patel AB, Lai JCK, Chowdhury GMI, Hyder F, Rothman DL, Shulman RG, Behar KL (2014) Direct evidence for activity-dependent glucose phosphorylation in neurons with implications for the astrocyte-to-neuron lactate shuttle. Proc Natl Acad Sci U S A 111:5385–5390. https://doi.org/10.1073/pnas.1403576111

Díaz-García CM, Mongeon R, Lahmann C, Koveal D, Zucker H, Yellen G (2017) Neuronal Stimulation Triggers Neuronal Glycolysis and Not Lactate Uptake. Cell Metabol 26:361–374. https://doi.org/10.1016/j.cmet.2017.06.021

Ivanov AI, Malkov AE, Waseem T, Mukhtarov M, Buldakova S, Gubkina O, Zilberter M, Zilberter Y (2014) Glycolysis and Oxidative Phosphorylation in Neurons and Astrocytes during Network Activity in Hippocampal Slices. J Cereb Blood Flow Metab 34:397–407. https://doi.org/10.1038/jcbfm.2013.222

Tang BL (2018) Brain activity-induced neuronal glucose uptake/glycolysis: Is the lactate shuttle not required? Brain Res Bull 137:225–228. https://doi.org/10.1016/j.brainresbull.2017.12.010

Swanson RA, Yu ACH, Chan PH, Sharp FR (1990) Glutamate Increases Glycogen Content and Reduces Glucose Utilization in Primary Astrocyte Culture. J Neurochem 54:490–496. https://doi.org/10.1111/j.1471-4159.1990.tb01898.x

Sickmann HM, Walls AB, Schousboe A, Bouman SD, Waagepetersen HS (2009) Functional significance of brain glycogen in sustaining glutamatergic neurotransmission. J Neurochem 109:80–86. https://doi.org/10.1111/j.1471-4159.2009.05915.x

Xu J, Song D, Xue Z, Gu L, Hertz L, Peng L (2013) Requirement of Glycogenolysis for Uptake of Increased Extracellular K+ in Astrocytes: Potential Implications for K+ Homeostasis and Glycogen Usage in Brain. Neurochem Res 38:472–485. https://doi.org/10.1007/s11064-012-0938-3

Tekkök SB, Brown AM, Westenbroek R, Pellerin L, Ransom BR (2005) Transfer of glycogen-derived lactate from astrocytes to axons via specific monocarboxylate transporters supports mouse optic nerve activity. J Neurosci Res 81:644–652. https://doi.org/10.1002/jnr.20573

Bak LK, Walls AB, Schousboe A, Waagepetersen HS (2018) Astrocytic glycogen metabolism in the healthy and diseased brain. J Biol Chem 293:7108–7116. https://doi.org/10.1074/jbc.R117.803239

van Deijk A-LF, Camargo N, Timmerman J, Heistek T, Brouwers JF, Mogavero F, Mansvelder HD, Smit AB, Verheijen MHG (2017) Astrocyte lipid metabolism is critical for synapse development and function in vivo. Glia 65:670–682. https://doi.org/10.1002/glia.23120

Camargo N, Goudriaan A, van Deijk A-LF, Otte WM, Brouwers JF, Lodder H, Gutmann DH, Nave K-A, Dijkhuizen RM, Mansvelder HD, Chrast R, Smit AB, Verheijen MHG (2017) Oligodendroglial myelination requires astrocyte-derived lipids. PLoS Biol 15:e1002605. https://doi.org/10.1371/journal.pbio.1002605

Martin PM, Gopal E, Ananth S, Zhuang L, Itagaki S, Prasad BM, Smith SB, Prasad PD, Ganapathy V (2006) Identity of SMCT1 (SLC5A8) as a neuron-specific Na+-coupled transporter for active uptake of l-lactate and ketone bodies in the brain. J Neurochem 98:279–288. https://doi.org/10.1111/j.1471-4159.2006.03878.x

Brunner B, Rauch E, Ari C, D’Agostino DP, Kovács Z (2021) Enhancement of Ketone Supplements-Evoked Effect on Absence Epileptic Activity by Co-Administration of Uridine in Wistar Albino jGlaxo Riswijk Rats. Nutrients 13:234. https://doi.org/10.3390/nu13010234

Deng-Bryant Y, Prins ML, Hovda DA, Harris NG (2011) Ketogenic Diet Prevents Alterations in Brain Metabolism in Young but not Adult Rats after Traumatic Brain Injury. J Neurotrauma 28:1813–1825. https://doi.org/10.1089/neu.2011.1822

Takahashi S, Iizumi T, Mashima K, Abe T, Suzuki N (2014) Roles and Regulation of Ketogenesis in Cultured Astroglia and Neurons Under Hypoxia and Hypoglycemia. ASN Neuro 6:175909141455099. https://doi.org/10.1177/1759091414550997

Itoh Y, Esaki T, Shimoji K, Cook M, Law MJ, Kaufman E, Sokoloff L (2003) Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo. Proc Natl Acad Sci U S A 100:4879–4884. https://doi.org/10.1073/pnas.0831078100

Abe T, Takahashi S, Suzuki N (2006) Oxidative Metabolism in Cultured Rat Astroglia: Effects of Reducing the Glucose Concentration in the Culture Medium and of D-Aspartate or Potassium Stimulation. J Cereb Blood Flow Metab 26:153–160. https://doi.org/10.1038/sj.jcbfm.9600175

Lebon V, Petersen KF, Cline GW, Shen J, Mason GF, Dufour S, Behar KL, Shulman GI, Rothman DL (2002) Astroglial Contribution to Brain Energy Metabolism in Humans Revealed by 13 C Nuclear Magnetic Resonance Spectroscopy: Elucidation of the Dominant Pathway for Neurotransmitter Glutamate Repletion and Measurement of Astrocytic Oxidative Metabolism. J Neurosci 22:1523–1531. https://doi.org/10.1523/JNEUROSCI.22-05-01523.2002

Takado Y, Knott G, Humbel BM, Escrig S, Masoodi M, Meibom A, Comment A (2015) Imaging liver and brain glycogen metabolism at the nanometer scale. Nanomedicine: Nanotechnology, Biology and Medicine 11:239–245. https://doi.org/10.1016/j.nano.2014.09.007

Walls AB, Heimbürger CM, Bouman SD, Schousboe A, Waagepetersen HS (2009) Robust glycogen shunt activity in astrocytes: Effects of glutamatergic and adrenergic agents. Neuroscience 158:284–292. https://doi.org/10.1016/j.neuroscience.2008.09.058

Suh SW, Bergher JP, Anderson CM, Treadway JL, Fosgerau K, Swanson RA (2007) Astrocyte Glycogen Sustains Neuronal Activity during Hypoglycemia: Studies with the Glycogen Phosphorylase Inhibitor CP-316,819 ([ R - R *, S *]-5-Chloro- N -[2-hydroxy-3-(methoxymethylamino)-3-oxo-1-(phenylmethyl)propyl]-1 H -indole-2-carboxamide). J Pharmacol Exp Ther 321:45–50. https://doi.org/10.1124/jpet.106.115550

Choi I-Y, Seaquist ER, Gruetter R (2003) Effect of hypoglycemia on brain glycogen metabolism in vivo. J Neurosci Res 72:25–32. https://doi.org/10.1002/jnr.10574

Kong J, Shepel PN, Holden CP, Mackiewicz M, Pack AI, Geiger JD (2002) Brain Glycogen Decreases with Increased Periods of Wakefulness: Implications for Homeostatic Drive to Sleep. J Neurosci 22:5581–5587. https://doi.org/10.1523/JNEUROSCI.22-13-05581.2002

Brown AM, Tekkök SB, Ransom BR (2003) Glycogen Regulation and Functional Role in Mouse White Matter. J Physiol 549:501–512. https://doi.org/10.1113/jphysiol.2003.042416

Cardinaux JR, Allaman I, Magistretti PJ (2000) Pro-inflammatory cytokines induce the transcription factors C/EBPbeta and C/EBPdelta in astrocytes. Glia 29:91–97.

Petit J-M, Tobler I, Allaman I, Borbély AA, Magistretti PJ (2002) Sleep deprivation modulates brain mRNAs encoding genes of glycogen metabolism: Sleep and brain glycogen metabolism. Eur J Neurosci 16:1163–1167. https://doi.org/10.1046/j.1460-9568.2002.02145.x

Wahis J, Holt MG (2021) Astrocytes, Noradrenaline, α1-Adrenoreceptors, and Neuromodulation: Evidence and Unanswered Questions. Front Cell Neurosci 15:645691. https://doi.org/10.3389/fncel.2021.645691

Hertz L, Lovatt D, Goldman SA, Nedergaard M (2010) Adrenoceptors in brain: Cellular gene expression and effects on astrocytic metabolism and [Ca2+]i. Neurochem Int 57:411–420. https://doi.org/10.1016/j.neuint.2010.03.019

Vardjan N, Horvat A, Anderson JE, Yu D, Croom D, Zeng X, Lužnik Z, Kreft M, Teng YD, Kirov SA, Zorec R (2016) Adrenergic activation attenuates astrocyte swelling induced by hypotonicity and neurotrauma: Adrenergic Activation Reduces Astrocyte Swelling. Glia 64(6):1034-1049. https://doi.org/10.1002/glia.22981

Vardjan N, Chowdhury HH, Horvat A, Velebit J, Malnar M, Muhič M, Kreft M, Krivec ŠG, Bobnar ST, Miš K, Pirkmajer S, Offermanns S, Henriksen G, Storm-Mathisen J, Bergersen LH, Zorec R (2018) Enhancement of Astroglial Aerobic Glycolysis by Extracellular Lactate-Mediated Increase in cAMP. Front Mol Neurosci 11:148. https://doi.org/10.3389/fnmol.2018.00148

Chalermpalanupap T, Schroeder JP, Rorabaugh JM, Liles LC, Lah JJ, Levey AI, Weinshenker D (2018) Locus Coeruleus Ablation Exacerbates Cognitive Deficits, Neuropathology, and Lethality in P301S Tau Transgenic Mice. J Neurosci 38:74–92. https://doi.org/10.1523/JNEUROSCI.1483-17.2017

Harris RA, Lone A, Lim H, Martinez F, Frame AK, Scholl TJ, Cumming RC (2019) Aerobic Glycolysis Is Required for Spatial Memory Acquisition But Not Memory Retrieval in Mice. eNeuro 6:ENEURO.0389-18.2019. https://doi.org/10.1523/ENEURO.0389-18.2019

Gibbs ME, Hutchinson DS, Summers RJ (2010) Noradrenaline release in the locus coeruleus modulates memory formation and consolidation; roles for α- and β-adrenergic receptors. Neuroscience 170:1209–1222. https://doi.org/10.1016/j.neuroscience.2010.07.052

Rothman DL, Dienel GA (2019) Development of a Model to Test Whether Glycogenolysis Can Support Astrocytic Energy Demands of Na+, K+-ATPase and Glutamate-Glutamine Cycling, Sparing an Equivalent Amount of Glucose for Neurons. In: DiNuzzo M, Schousboe A (eds) Brain Glycogen Metabolism. Springer Int Publ, Cham 385–433.

Bolton CJ, Tam JW (2020) Differential Involvement of the Locus Coeruleus in Early- and Late-Onset Alzheimer’s Disease: A Potential Mechanism of Clinical Differences? Neurology. https://doi.org/10.1101/2020.11.01.20224139

Chuquet J, Quilichini P, Nimchinsky EA, Buzsaki G (2010) Predominant Enhancement of Glucose Uptake in Astrocytes versus Neurons during Activation of the Somatosensory Cortex. J Neurosci 30:15298–15303. https://doi.org/10.1523/JNEUROSCI.0762-10.2010

Wang Q, Hu Y, Wan J, Dong B, Sun J (2019) Lactate: A Novel Signaling Molecule in Synaptic Plasticity and Drug Addiction. BioEssays 41:1900008. https://doi.org/10.1002/bies.201900008

Magistretti PJ, Allaman I (2015) A Cellular Perspective on Brain Energy Metabolism and Functional Imaging. Neuron 86:883–901. https://doi.org/10.1016/j.neuron.2015.03.035

Hui S, Ghergurovich JM, Morscher RJ, Jang C, Teng X, Lu W, Esparza LA, Reya T, Le Zhan, Yanxiang Guo J, White E, Rabinowitz JD (2017) Glucose feeds the TCA cycle via circulating lactate. Nature 551:115–118. https://doi.org/10.1038/nature24057

DiNuzzo M, Giove F, Maraviglia B, Mangia S (2017) Computational Flux Balance Analysis Predicts that Stimulation of Energy Metabolism in Astrocytes and their Metabolic Interactions with Neurons Depend on Uptake of K+ Rather than Glutamate. Neurochem Res 42:202–216. https://doi.org/10.1007/s11064-016-2048-0

Boury-Jamot B, Carrard A, Martin JL, Halfon O, Magistretti PJ, Boutrel B (2016) Disrupting astrocyte–neuron lactate transfer persistently reduces conditioned responses to cocaine. Mol Psychiatry 21:1070–1076. https://doi.org/10.1038/mp.2015.157

Newman LA, Korol DL, Gold PE (2011) Lactate Produced by Glycogenolysis in Astrocytes Regulates Memory Processing. PLoS ONE 6:e28427. https://doi.org/10.1371/journal.pone.0028427

Margineanu MB, Mahmood H, Fiumelli H, Magistretti PJ (2018) L-Lactate Regulates the Expression of Synaptic Plasticity and Neuroprotection Genes in Cortical Neurons: A Transcriptome Analysis. Front Mol Neurosci 11:375. https://doi.org/10.3389/fnmol.2018.00375

Herrera-López G, Griego E, Galván EJ (2020) Lactate induces synapse-specific potentiation on CA3 pyramidal cells of rat hippocampus. PLoS ONE 15:e0242309. https://doi.org/10.1371/journal.pone.0242309

Yang J, Ruchti E, Petit J-M, Jourdain P, Grenningloh G, Allaman I, Magistretti PJ (2014) Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons. Proc Natl Acad Sci U S A 111:12228–12233. https://doi.org/10.1073/pnas.1322912111

Newman LA, Scavuzzo CJ, Gold PE, Korol DL (2017) Training-induced elevations in extracellular lactate in hippocampus and striatum: Dissociations by cognitive strategy and type of reward. Neurobiol Learning and Memory 137:142–153. https://doi.org/10.1016/j.nlm.2016.12.001

Pötzsch A, Zocher S, Bernas SN, Leiter O, Rünker AE, Kempermann G (2021) L-lactate exerts a pro-proliferative effect on adult hippocampal precursor cells in vitro. Science 24:102126. https://doi.org/10.1016/j.isci.2021.102126

Ruchti E, Roach PJ, DePaoli-Roach AA, Magistretti PJ, Allaman I (2016) Protein targeting to glycogen is a master regulator of glycogen synthesis in astrocytes. IBRO Reports 1:46–53. https://doi.org/10.1016/j.ibror.2016.10.002

Magistretti PJ, Dietl MM, Hof PR, Martin J-L, Palacios JM, Schaad N, Schorderet M (1988) Vasoactive Intestinal Peptide as a Mediator of Intercellular Communication in the Cerebral Cortex. Release, Receptors, Actions, and Interactions with Norepinephrine. Ann NY Acad Sci 527:110–129. https://doi.org/10.1111/j.1749-6632.1988.tb26977.x

Coggan JS, Keller D, Calì C, Lehväslaiho H, Markram H, Schürmann F, Magistretti PJ (2018) Norepinephrine stimulates glycogenolysis in astrocytes to fuel neurons with lactate. PLoS Comput Biol 14:e1006392. https://doi.org/10.1371/journal.pcbi.1006392

Gao V, Suzuki A, Magistretti PJ, Lengacher S, Pollonini G, Steinman MQ, Alberini CM (2016) Astrocytic β 2 -adrenergic receptors mediate hippocampal long-term memory consolidation. Proc Natl Acad Sci U S A 113:8526–8531. https://doi.org/10.1073/pnas.1605063113

Walls AB, Sickmann HM, Brown A, Bouman SD, Ransom B, Schousboe A, Waagepetersen HS (2008) Characterization of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) as an inhibitor of brain glycogen shunt activity. J Neurochem 105:1462–1470. https://doi.org/10.1111/j.1471-4159.2008.05250.x

Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM (2011) Astrocyte-Neuron Lactate Transport Is Required for Long-Term Memory Formation. Cell 144:810–823. https://doi.org/10.1016/j.cell.2011.02.018

Vezzoli E, Calì C, De Roo M, Ponzoni L, Sogne E, Gagnon N, Francolini M, Braida D, Sala M, Muller D, Falqui A, Magistretti PJ (2020) Ultrastructural Evidence for a Role of Astrocytes and Glycogen-Derived Lactate in Learning-Dependent Synaptic Stabilization. Cerebr Cortex 30:2114–2127. https://doi.org/10.1093/cercor/bhz226

Edmond J, Robbins RA, Bergstrom JD, Cole RA, de Vellis J (1987) Capacity for substrate utilization in oxidative metabolism by neurons, astrocytes, and oligodendrocytes from developing brain in primary culture. J Neurosci Res 18:551–561. https://doi.org/10.1002/jnr.490180407

Ebert D, Haller RG, Walton ME (2003) Energy Contribution of Octanoate to Intact Rat Brain Metabolism Measured by 13 C Nuclear Magnetic Resonance Spectroscopy. J Neurosci 23:5928–5935. https://doi.org/10.1523/JNEUROSCI.23-13-05928.2003

Hardie DG (2008) AMPK: a key regulator of energy balance in the single cell and the whole organism. Int J Obes 32:S7–S12. https://doi.org/10.1038/ijo.2008.116

Blázquez C, Woods A, De Ceballos ML, Carling D, Guzmán M (2002) The AMP-Activated Protein Kinase Is Involved in the Regulation of Ketone Body Production by Astrocytes. J Neurochem 73:1674–1682. https://doi.org/10.1046/j.1471-4159.1999.731674.x

Westhaus A, Blumrich EM, Dringen R (2017) The Antidiabetic Drug Metformin Stimulates Glycolytic Lactate Production in Cultured Primary Rat Astrocytes. Neurochem Res 42:294–305. https://doi.org/10.1007/s11064-015-1733-8

Takahashi S (2020) Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit. Neuropathology 40:121–137. https://doi.org/10.1111/neup.12639

Le Foll C, Levin BE (2016) Fatty acid-induced astrocyte ketone production and the control of food intake. Am J Physiol Regulat, Integrativ and Compar Physiol 310:R1186–R1192. https://doi.org/10.1152/ajpregu.00113.2016

Youssef FF (2015) Ketone bodies attenuate excitotoxic cell injury in the rat hippocampal slice under conditions of reduced glucose availability. Neurol Res 37:211–216. https://doi.org/10.1179/1743132814Y.0000000430

Prins ML (2008) Cerebral Metabolic Adaptation and Ketone Metabolism after Brain Injury. J Cereb Blood Flow Metab 28:1–16. https://doi.org/10.1038/sj.jcbfm.9600543

Samoilova M, Weisspapir M, Abdelmalik P, Velumian AA, Carlen PL (2010) Chronic in vitro ketosis is neuroprotective but not anti-convulsant. J Neurochem 113:826–835. https://doi.org/10.1111/j.1471-4159.2010.06645.x

Błaszczyk JW (2020) Energy Metabolism Decline in the Aging Brain—Pathogenesis of Neurodegenerative Disorders. Metabolites 10:450. https://doi.org/10.3390/metabo10110450

Cunnane SC, Courchesne-Loyer A, Vandenberghe C, St-Pierre V, Fortier M, Hennebelle M, Croteau E, Bocti C, Fulop T, Castellano C-A (2016) Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer’s Disease. Front Mol Neurosci 9. https://doi.org/10.3389/fnmol.2016.00053

Pellerin L, Halestrap AP, Pierre K (2005) Cellular and subcellular distribution of monocarboxylate transporters in cultured brain cells and in the adult brain. J Neurosci Res 79:55–64. https://doi.org/10.1002/jnr.20307

Hawkins RA, Mans AM, Davis DW (1986) Regional ketone body utilization by rat brain in starvation and diabetes. Am J Physiol Endocrinol Metabol 250:E169–E178. https://doi.org/10.1152/ajpendo.1986.250.2.E169

Pan JW, Telang FW, Lee JH, De Graaf RA, Rothman DL, Stein DT, Hetherington HP (2008) Measurement of β-hydroxybutyrate in acute hyperketonemia in human brain: Cerebral BHB in acute hyperketonemia. J Neurochem 79:539–544. https://doi.org/10.1046/j.1471-4159.2001.00575.x

Hargrave SL, Davidson TL, Lee T-J, Kinzig KP (2015) Brain and behavioral perturbations in rats following Western diet access. Appetite 93:35–43. https://doi.org/10.1016/j.appet.2015.03.037

Leino RL, Gerhart DZ, Duelli R, Enerson BE, Drewes LR (2001) Diet-induced ketosis increases monocarboxylate transporter (MCT1) levels in rat brain. Neurochem Int 38:519–527. https://doi.org/10.1016/S0197-0186(00)00102-9

Takimoto M, Hamada T (2014) Acute exercise increases brain region-specific expression of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins. J Appl Physiol 116:1238–1250. https://doi.org/10.1152/japplphysiol.01288.2013

Escartin C, Pierre K, Colin A, Brouillet E, Delzescaux T, Guillermier M, Dhenain M, Deglon N, Hantraye P, Pellerin L, Bonvento G (2007) Activation of Astrocytes by CNTF Induces Metabolic Plasticity and Increases Resistance to Metabolic Insults. J Neurosci 27:7094–7104. https://doi.org/10.1523/JNEUROSCI.0174-07.2007

Phillis JW, O’Regan MH (2004) A potentially critical role of phospholipases in central nervous system ischemic, traumatic, and neurodegenerative disorders. Brain Res Rev 44:13–47. https://doi.org/10.1016/j.brainresrev.2003.10.002

Sun GY, Xu J, Jensen MD, Simonyi A (2004) Phospholipase A2 in the central nervous system. J Lipid Res 45:205–213. https://doi.org/10.1194/jlr.R300016-JLR200

Dhillon VS, Fenech M (2014) Mutations that affect mitochondrial functions and their association with neurodegenerative diseases. Mutation Res/Rev in Mutation Res 759:1–13. https://doi.org/10.1016/j.mrrev.2013.09.001

Yan L-J, Xiao M, Chen R, Cai Z (2013) Metabolic Dysfunction of Astrocyte: An Initiating Factor in Beta-amyloid Pathology? Aging Neurodegener 1:7–14.

Nadler Y, Alexandrovich A, Grigoriadis N, Hartmann T, Rao KSJ, Shohami E, Stein R (2008) Increased expression of the γ-secretase components presenilin-1 and nicastrin in activated astrocytes and microglia following traumatic brain injury. Glia 56:552–567. https://doi.org/10.1002/glia.20638

Perdivara I, Petrovich R, Allinquant B, Deterding LJ, Tomer KB, Przybylski M (2009) Elucidation of O-Glycosylation Structures of the β-Amyloid Precursor Protein by Liquid Chromatography−Mass Spectrometry Using Electron Transfer Dissociation and Collision Induced Dissociation. J Proteome Res 8:631–642. https://doi.org/10.1021/pr800758g

Allaman I, Gavillet M, Belanger M, Laroche T, Viertl D, Lashuel HA, Magistretti PJ (2010) Amyloid- Aggregates Cause Alterations of Astrocytic Metabolic Phenotype: Impact on Neuronal Viability. J Neurosci 30:3326–3338. https://doi.org/10.1523/JNEUROSCI.5098-09.2010

Yin X, Feng L, Ma D, Yin P, Wang X, Hou S, Hao Y, Zhang J, Xin M, Feng J (2018) Roles of astrocytic connexin-43, hemichannels, and gap junctions in oxygen-glucose deprivation/reperfusion injury induced neuroinflammation and the possible regulatory mechanisms of salvianolic acid B and carbenoxolone. J Neuroinflammat 15:97. https://doi.org/10.1186/s12974-018-1127-3

Iglesias J, Morales L, Barreto GE (2017) Metabolic and Inflammatory Adaptation of Reactive Astrocytes: Role of PPARs. Mol Neurobiol 54:2518–2538. https://doi.org/10.1007/s12035-016-9833-2

Zecca L, Wilms H, Geick S, Claasen J-H, Brandenburg L-O, Holzknecht C, Panizza ML, Zucca FA, Deuschl G, Sievers J, Lucius R (2008) Human neuromelanin induces neuroinflammation and neurodegeneration in the rat substantia nigra: implications for Parkinson’s disease. Acta Neuropathol 116:47–55. https://doi.org/10.1007/s00401-008-0361-7

Bellucci A, Collo G, Sarnico I, Battistin L, Missale C, Spano P (2008) Alpha-synuclein aggregation and cell death triggered by energy deprivation and dopamine overload are counteracted by D 2 D 3 receptor activation. J Neurochem 106:560–577. https://doi.org/10.1111/j.1471-4159.2008.05406.x

Jiang P, Gan M, Ebrahim AS, Castanedes-Casey M, Dickson DW, Yen S-HC (2013) Adenosine monophosphate-activated protein kinase overactivation leads to accumulation of α-synuclein oligomers and decrease of neurites. Neurobiol Aging 34:1504–1515. https://doi.org/10.1016/j.neurobiolaging.2012.11.001

Schmidt S, Linnartz B, Mendritzki S, Sczepan T, Lubbert M, Stichel CC, Lubbert H (2011) Genetic mouse models for Parkinson’s disease display severe pathology in glial cell mitochondria. Human Mol Genetics 20:1197–1211. https://doi.org/10.1093/hmg/ddq564

Gu X-L, Long C-X, Sun L, Xie C, Lin X, Cai H (2010) Astrocytic expression of Parkinson’s disease-related A53T α-synuclein causes neurodegeneration in mice. Mol Brain 3:12. https://doi.org/10.1186/1756-6606-3-12

Tsai MJ, Lee EH (1996) Characterization of L-DOPA transport in cultured rat and mouse astrocytes. J Neurosci Res 43:490–495. https://doi.org/10.1002/(SICI)1097-4547(19960215)43:4<490::AID-JNR10>3.0.CO;2-6

Asanuma M, Miyazaki I, Murakami S, Diaz-Corrales FJ, Ogawa N (2014) Striatal Astrocytes Act as a Reservoir for L-DOPA. PLoS ONE 9:e106362. https://doi.org/10.1371/journal.pone.0106362

Wójtowicz AM, Dvorzhak A, Semtner M, Grantyn R (2013) Reduced tonic inhibition in striatal output neurons from Huntington mice due to loss of astrocytic GABA release through GAT-3. Front Neural Circuits 7. https://doi.org/10.3389/fncir.2013.00188

Lee W, Reyes RC, Gottipati MK, Lewis K, Lesort M, Parpura V, Gray M (2013) Enhanced Ca2+-dependent glutamate release from astrocytes of the BACHD Huntington’s disease mouse model. Neurobiol Disease 58:192–199. https://doi.org/10.1016/j.nbd.2013.06.002

Madji Hounoum B, Mavel S, Coque E, Patin F, Vourc’h P, Marouillat S, Nadal-Desbarats L, Emond P, Corcia P, Andres CR, Raoul C, Blasco H (2017) Wildtype motoneurons, ALS-Linked SOD1 mutation and glutamate profoundly modify astrocyte metabolism and lactate shuttling: Astrocyte Metabolism in ALS-Associated Conditions. Glia 65:592–605. https://doi.org/10.1002/glia.23114

Mitropoulos K, Katsila T, Patrinos GP, Pampalakis G (2018) Multi-Omics for Biomarker Discovery and Target Validation in Biofluids for Amyotrophic Lateral Sclerosis Diagnosis. OMICS: J Integr Biol 22:52–64. https://doi.org/10.1089/omi.2017.0183

Cistaro A, Valentini MC, Chiò A, Nobili F, Calvo A, Moglia C, Montuschi A, Morbelli S, Salmaso D, Fania P, Carrara G, Pagani M (2012) Brain hypermetabolism in amyotrophic lateral sclerosis: a FDG PET study in ALS of spinal and bulbar onset. Eur J Nucl Med Mol Imaging 39:251–259. https://doi.org/10.1007/s00259-011-1979-6

Ferraiuolo L, Higginbottom A, Heath PR, Barber S, Greenald D, Kirby J, Shaw PJ (2011) Dysregulation of astrocyte–motoneuron cross-talk in mutant superoxide dismutase 1-related amyotrophic lateral sclerosis. Brain 134:2627–2641. https://doi.org/10.1093/brain/awr193