Metabolic changes favor the activity and heterogeneity of reactive astrocytes

Kimelberg, 2010, Functions of astrocytes and their potential as therapeutic targets, Neurotherapeutics, 7, 338, 10.1016/j.nurt.2010.07.006 Iadecola, 2007, Glial regulation of the cerebral microvasculature, Nat. Neurosci., 10, 1369, 10.1038/nn2003 Oberheim, 2008, Loss of astrocytic domain organization in the epileptic brain, J. Neurosci., 28, 3264, 10.1523/JNEUROSCI.4980-07.2008 Oberheim, 2009, Uniquely hominid features of adult human astrocytes, J. Neurosci., 29, 3276, 10.1523/JNEUROSCI.4707-08.2009 Ji, 2013, Glia and pain: is chronic pain a gliopathy?, Pain, 154, S10, 10.1016/j.pain.2013.06.022 Langen, 2019, Development and cell biology of the blood–brain barrier, Annu. Rev. Cell Dev. Biol., 35, 591, 10.1146/annurev-cellbio-100617-062608 Verkhratsky, 2018, Physiology of astroglia, Physiol. Rev., 98, 239, 10.1152/physrev.00042.2016 Burda, 2016, Astrocyte roles in traumatic brain injury, Exp. Neurol., 275, 305, 10.1016/j.expneurol.2015.03.020 Sofroniew, 2014, Astrogliosis, Cold Spring Harb. Perspect. Biol., 7 Escartin, 2019, Questions and (some) answers on reactive astrocytes, Glia, 67, 2221, 10.1002/glia.23687 Itoh, 2018, Cell-specific and region-specific transcriptomics in the multiple sclerosis model: Focus on astrocytes, Proc. Natl. Acad. Sci. U. S. A., 115, E302, 10.1073/pnas.1716032115 Anderson, 2016, Astrocyte scar formation aids central nervous system axon regeneration, Nature, 532, 195, 10.1038/nature17623 Diaz-Castro, 2019, Astrocyte molecular signatures in Huntington's disease, Sci. Transl. Med., 11, eaaw8546, 10.1126/scitranslmed.aaw8546 Zamanian, 2012, Genomic analysis of reactive astrogliosis, J. Neurosci., 32, 6391, 10.1523/JNEUROSCI.6221-11.2012 Escartin, 2021, Reactive astrocyte nomenclature, definitions, and future directions, Nat. Neurosci., 24, 312, 10.1038/s41593-020-00783-4 Lemoine, 2017, Cortical laminar tau deposits and activated astrocytes in Alzheimer's disease visualised by (3)H-THK5117 and (3)H-deprenyl autoradiography, Sci. Rep., 7, 45496, 10.1038/srep45496 Heneka, 2010, Neuroglia in neurodegeneration, Brain Res. Rev., 63, 189, 10.1016/j.brainresrev.2009.11.004 Liddelow, 2017, Neurotoxic reactive astrocytes are induced by activated microglia, Nature, 541, 481, 10.1038/nature21029 Williamson, 2021, Reactive astrocytes facilitate vascular repair and remodeling after stroke, Cell Rep., 35, 10.1016/j.celrep.2021.109048 Mayo, 2014, Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation, Nat. Med., 20, 1147, 10.1038/nm.3681 Gomez-Arboledas, 2018, Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease, Glia, 66, 637, 10.1002/glia.23270 Wakida, 2018, Phagocytic response of astrocytes to damaged neighboring cells, PLoS One, 13, 10.1371/journal.pone.0196153 Smith, 2020, Astrocyte unfolded protein response induces a specific reactivity state that causes non-cell-autonomous neuronal degeneration, Neuron, 105, 855, 10.1016/j.neuron.2019.12.014 Blazquez, 1999, The AMP-activated protein kinase is involved in the regulation of ketone body production by astrocytes, J. Neurochem., 73, 1674, 10.1046/j.1471-4159.1999.731674.x Magistretti, 2018, Lactate in the brain: from metabolic end-product to signalling molecule, Nat. Rev. Neurosci., 19, 235, 10.1038/nrn.2018.19 Wender, 2000, Astrocytic glycogen influences axon function and survival during glucose deprivation in central white matter, J. Neurosci., 20, 6804, 10.1523/JNEUROSCI.20-18-06804.2000 Dienel, 2016, Aerobic glycolysis during brain activation: adrenergic regulation and influence of norepinephrine on astrocytic metabolism, J. Neurochem., 138, 14, 10.1111/jnc.13630 Goyal, 2014, Aerobic glycolysis in the human brain is associated with development and neotenous gene expression, Cell Metab., 19, 49, 10.1016/j.cmet.2013.11.020 Supplie, 2017, Respiration-deficient astrocytes survive as glycolytic cells in vivo, J. Neurosci., 37, 4231, 10.1523/JNEUROSCI.0756-16.2017 Itoh, 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, 10.1073/pnas.0831078100 Lovatt, 2007, The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex, J. Neurosci., 27, 12255, 10.1523/JNEUROSCI.3404-07.2007 Lopez-Fabuel, 2016, Complex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes, Proc. Natl. Acad. Sci. U. S. A., 113, 13063, 10.1073/pnas.1613701113 Dienel, 2019, Brain glucose metabolism: integration of energetics with function, Physiol. Rev., 99, 949, 10.1152/physrev.00062.2017 Niitsu, 1999, Exposure of cultured primary rat astrocytes to hypoxia results in intracellular glucose depletion and induction of glycolytic enzymes, Brain Res. Mol. Brain Res., 74, 26, 10.1016/S0169-328X(99)00245-4 Zheng, 2021, GLP-1 improves the supportive ability of astrocytes to neurons by promoting aerobic glycolysis in Alzheimer's disease, Mol. Metab., 47, 10.1016/j.molmet.2021.101180 Fu, 2015, Bioenergetic mechanisms in astrocytes may contribute to amyloid plaque deposition and toxicity, J. Biol. Chem., 290, 12504, 10.1074/jbc.M114.618157 Pamies, 2021, Neuroinflammatory response to TNFα and IL1β cytokines is accompanied by an increase in glycolysis in human astrocytes in vitro, Int. J. Mol. Sci., 22, 4065, 10.3390/ijms22084065 Robb, 2020, The metabolic response to inflammation in astrocytes is regulated by nuclear factor-kappa B signaling, Glia, 68, 2246, 10.1002/glia.23835 Zhang, 2014, An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex, J. Neurosci., 34, 11929, 10.1523/JNEUROSCI.1860-14.2014 Pilkis, 1995, 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: a metabolic signaling enzyme, Annu. Rev. Biochem., 64, 799, 10.1146/annurev.bi.64.070195.004055 Rider, 2004, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis, Biochem. J., 381, 561, 10.1042/BJ20040752 Li, 2018, Acetylation accumulates PFKFB3 in cytoplasm to promote glycolysis and protects cells from cisplatin-induced apoptosis, Nat. Commun., 9, 508, 10.1038/s41467-018-02950-5 Lv, 2015, PFKFB3-mediated glycolysis is involved in reactive astrocyte proliferation after oxygen–glucose deprivation/reperfusion and is regulated by Cdh1, Neurochem. Int., 91, 26, 10.1016/j.neuint.2015.10.006 Wei, 2020, Pyridoxine induces glutathione synthesis via PKM2-mediated Nrf2 transactivation and confers neuroprotection, Nat. Commun., 11, 941, 10.1038/s41467-020-14788-x Mazurek, 2005, Pyruvate kinase type M2 and its role in tumor growth and spreading, Semin. Cancer Biol., 15, 300, 10.1016/j.semcancer.2005.04.009 Zhang, 2015, Nuclear translocation of PKM2 modulates astrocyte proliferation via p27 and β-catenin pathway after spinal cord injury, Cell Cycle, 14, 2609, 10.1080/15384101.2015.1064203 Lunt, 2015, Pyruvate kinase isoform expression alters nucleotide synthesis to impact cell proliferation, Mol. Cell, 57, 95, 10.1016/j.molcel.2014.10.027 Israelsen, 2015, Pyruvate kinase: Function, regulation and role in cancer, Semin. Cell Dev. Biol., 43, 43, 10.1016/j.semcdb.2015.08.004 Luo, 2011, Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1, Cell, 145, 732, 10.1016/j.cell.2011.03.054 Angiari, 2020, Pharmacological activation of pyruvate kinase M2 Inhibits CD4(+) T cell pathogenicity and suppresses autoimmunity, Cell Metab., 31, 391, 10.1016/j.cmet.2019.10.015 Yang, 2014, PKM2 regulates the Warburg effect and promotes HMGB1 release in sepsis, Nat. Commun., 5, 4436, 10.1038/ncomms5436 Halford, 2017, New astroglial injury-defined biomarkers for neurotrauma assessment, J. Cereb. Blood Flow Metab., 37, 3278, 10.1177/0271678X17724681 Levine, 2016, Traumatically injured astrocytes release a proteomic signature modulated by STAT3-dependent cell survival, Glia, 64, 668, 10.1002/glia.22953 Asaka, 1990, Serum aldolase isozyme levels in patients with cerebrovascular diseases, Am J Med Sci, 300, 291, 10.1097/00000441-199011000-00004 Ebert, 2003, Energy contribution of octanoate to intact rat brain metabolism measured by 13C nuclear magnetic resonance spectroscopy, J. Neurosci., 23, 5928, 10.1523/JNEUROSCI.23-13-05928.2003 Kadish, 2009, Hippocampal and cognitive aging across the lifespan: a bioenergetic shift precedes and increased cholesterol trafficking parallels memory impairment, J. Neurosci., 29, 1805, 10.1523/JNEUROSCI.4599-08.2009 Kapogiannis, 2020, Brain glucose and ketone utilization in brain aging and neurodegenerative diseases, Int. Rev. Neurobiol., 154, 79, 10.1016/bs.irn.2020.03.015 Chocron, 2012, The trifunctional protein mediates thyroid hormone receptor-dependent stimulation of mitochondria metabolism, Mol. Endocrinol., 26, 1117, 10.1210/me.2011-1348 Sayre, 2017, Stimulation of astrocyte fatty acid oxidation by thyroid hormone is protective against ischemic stroke-induced damage, J. Cereb. Blood Flow Metab., 37, 514, 10.1177/0271678X16629153 Ioannou, 2019, Neuron–astrocyte metabolic coupling protects against activity-induced fatty acid toxicity, Cell, 177, 1522, 10.1016/j.cell.2019.04.001 Eraso-Pichot, 2018, GSEA of mouse and human mitochondriomes reveals fatty acid oxidation in astrocytes, Glia, 66, 1724, 10.1002/glia.23330 Polyzos, 2019, Metabolic reprogramming in astrocytes distinguishes region-specific neuronal susceptibility in Huntington mice, Cell Metab., 29, 1258, 10.1016/j.cmet.2019.03.004 Furuhashi, 2019, Fatty acid-binding protein 4 in cardiovascular and metabolic diseases, J. Atheroscler. Thromb., 26, 216, 10.5551/jat.48710 Boneva, 2010, Differential expression of FABP 3, 5, 7 in infantile and adult monkey cerebellum, Neurosci. Res., 68, 94, 10.1016/j.neures.2010.07.2028 Ebrahimi, 2016, Astrocyte-expressed FABP7 regulates dendritic morphology and excitatory synaptic function of cortical neurons, Glia, 64, 48, 10.1002/glia.22902 Watanabe, 2007, Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype, PLoS Biol., 5, 10.1371/journal.pbio.0050297 Islam, 2019, FABP7 protects astrocytes against ROS toxicity via lipid droplet formation, Mol. Neurobiol., 56, 5763, 10.1007/s12035-019-1489-2 Hara, 2020, Fatty acid binding protein 7 is involved in the proliferation of reactive astrocytes, but not in cell migration and polarity, Acta Histochem. Cytochem., 53, 73, 10.1267/ahc.20001 Kagawa, 2015, Fatty acid-binding protein 7 regulates function of caveolae in astrocytes through expression of caveolin-1, Glia, 63, 780, 10.1002/glia.22784 Killoy, 2020, FABP7 upregulation induces a neurotoxic phenotype in astrocytes, Glia, 68, 2693, 10.1002/glia.23879 Aizawa, 2016, Astrocytes release polyunsaturated fatty acids by lipopolysaccharide stimuli, Biol. Pharm. Bull., 39, 1100, 10.1248/bpb.b15-01037 Paterniti, 2014, Docosahexaenoic acid attenuates the early inflammatory response following spinal cord injury in mice: in-vivo and in-vitro studies, J. Neuroinflammation, 11, 6, 10.1186/1742-2094-11-6 Guttenplan, 2021, Neurotoxic reactive astrocytes induce cell death via saturated lipids, Nature, 599, 102, 10.1038/s41586-021-03960-y Gupta, 2012, Saturated long-chain fatty acids activate inflammatory signaling in astrocytes, J. Neurochem., 120, 1060, 10.1111/j.1471-4159.2012.07660.x Liu, 1999, Astrocytic demise precedes delayed neuronal death in focal ischemic rat brain, Brain Res. Mol. Brain Res., 68, 29, 10.1016/S0169-328X(99)00063-7 Garcia, 1977, Cellular events during partial cerebral ischemia. I. Electron microscopy of feline cerebral cortex after middle-cerebral-artery occlusion, Virchows Arch. B Cell Pathol., 25, 191, 10.1007/BF02889433 Fiebig, 2019, Mitochondrial dysfunction in astrocytes impairs the generation of reactive astrocytes and enhances neuronal cell death in the cortex upon photothrombotic lesion, Front. Mol. Neurosci., 12, 40, 10.3389/fnmol.2019.00040 Motori, 2013, Inflammation-induced alteration of astrocyte mitochondrial dynamics requires autophagy for mitochondrial network maintenance, Cell Metab., 18, 844, 10.1016/j.cmet.2013.11.005 Hayakawa, 2016, Transfer of mitochondria from astrocytes to neurons after stroke, Nature, 535, 551, 10.1038/nature18928 Joshi, 2019, Fragmented mitochondria released from microglia trigger A1 astrocytic response and propagate inflammatory neurodegeneration, Nat. Neurosci., 22, 1635, 10.1038/s41593-019-0486-0 Sayre, 2014, Purinergic receptor stimulation decreases ischemic brain damage by energizing astrocyte mitochondria, Adv. Neurobiol., 11, 121, 10.1007/978-3-319-08894-5_7 Cao, 2013, Astrocyte-derived ATP modulates depressive-like behaviors, Nat. Med., 19, 773, 10.1038/nm.3162 Yu, 2020, Improved tools to study astrocytes, Nat. Rev. Neurosci., 21, 121, 10.1038/s41583-020-0264-8 Miller, 1984, Fibrous and protoplasmic astrocytes are biochemically and developmentally distinct, J. Neurosci., 4, 585, 10.1523/JNEUROSCI.04-02-00585.1984