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Modulation of Inflammatory Cytokines and Mitogen-activated Protein Kinases by Acetate in Primary Astrocytes

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Abstract

Acetate supplementation attenuates neuroglia activation in a rat model of neuroinflammation by a mechanism associated with an increase in brain acetyl-CoA, an alteration in histone acetylation, and reduction of interleukin (IL)-1β expression. We propose that reduced astroglial activation occurs by disrupting astrocyte-derived inflammatory signaling and cytokine release. Using primary astroglial cultures, we found that LPS (0–25 ng/ml, 4 h) increased tumor necrosis factor (TNF-α) and IL-1β in a concentration-dependent manner, which was reduced by treatment with sodium acetate (12 mM). LPS did not alter H3K9 acetylation or IL-6 levels, whereas acetate treatment increased H3K9 acetylation by 2-fold and decreased basal levels of IL-6 by 2-fold. Acetate treatment attenuated the LPS-induced increase in TNF-α mRNA, but did not reverse the mRNA levels of other pro-inflammatory cytokines. By contrast, LPS decreased TGF-β1 and IL-4 protein and TGF-β1 mRNA, all of which was reversed with acetate treatment. Further, we found that acetate treatment completely reversed LPS-induced phosphorylation of MAPK p38 and decreased basal levels of phosphorylated extracellular signal-regulated kinases1/2 (ERK1/2) by 2-fold. Acetate treatment also reversed LPS-elevated NF-κB p65, CCAAT/enhancer-binding protein beta protein levels, and reduced basal levels of phosphorylated NF-κB p65 at serine 536. These results suggest that acetate treatment has a net anti-inflammatory effect in LPS-stimulated astrocytes that is largely associated with a disruption in MAPK and NF-κB signaling.

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References

  • Annunziato AT, Eason MB, Perry CA (1995) Relationship between methylation and acetylation of arginine-rich histones in cycling and arrested HeLa cells. Biochemistry 34:2916–2924

    Article  PubMed  CAS  Google Scholar 

  • Ariyannur PS, Moffett JR, Madhavarao CN, Arun P, Vishnu N, Jacobowitz DM, Hallows WC, Denu JM, Namboodiri AM (2010) Nuclear-cytoplasmic localization of acetyl coenzyme a synthetase-1 in the rat brain. J Comp Neurol 518:2952–2977

    Article  PubMed  CAS  Google Scholar 

  • Arun P, Ariyannur PS, Moffett JR, Xing G, Hamilton K, Grunberg NE, Ives JA, Namboodiri AM (2010a) Metabolic acetate therapy for the treatment of traumatic brain injury. J Neurotrauma 27:293–298

    Article  PubMed  Google Scholar 

  • Arun P, Madhavarao CN, Moffett JR, Hamilton K, Grunberg NE, Ariyannur PS, Gahl WA, Anikster Y, Mog S, Hallows WC, Denu JM, Namboodiri AM (2010b) Metabolic acetate therapy improves phenotype in the tremor rat model of Canavan disease. J Inherit Metab Dis 33:195–210

    Article  PubMed  Google Scholar 

  • Bannister AJ, Miska EA (2000) Regulation of gene expression by transcription factor acetylation. Cell Mol Life Sci 57:1184–1192

    Article  PubMed  CAS  Google Scholar 

  • Barone FC, Irving EA, Ray AM, Lee JC, Kassis S, Kumar S, Badger AM, White RF, McVey MJ, Legos JJ, Erhardt JA, Nelson AH, Ohlstein EH, Hunter AJ, Ward K, Smith BR, Adams JL, Parsons AA (2001) SB 239063, a second-generation p38 mitogen-activated protein kinase inhibitor, reduces brain injury and neurological deficits in cerebral focal ischemia. J Pharmacol Exp Ther 296:312–321

    PubMed  CAS  Google Scholar 

  • Bohuslav J, Chen LF, Kwon H, Mu Y, Greene WC (2004) p53 induces NF-kappaB activation by an IkappaB kinase-independent mechanism involving phosphorylation of p65 by ribosomal S6 kinase 1. J Biol Chem 279:26115–26125

    Article  PubMed  CAS  Google Scholar 

  • Brissette CA, Houdek HM, Floden AM, Rosenberger TA (2012) Acetate supplementation reduces microglia activation and brain interleukin-1beta levels in a rat model of Lyme neuroborreliosis. J Neuroinflammation 9:249

    Article  PubMed  CAS  Google Scholar 

  • Broer S, Rahman B, Pellegri G, Pellerin L, Martin JL, Verleysdonk S, Hamprecht B, Magistretti PJ (1997) Comparison of lactate transport in astroglial cells and monocarboxylate transporter 1 (MCT 1) expressing Xenopus laevis oocytes. Expression of two different monocarboxylate transporters in astroglial cells and neurons. J Biol Chem 272:30096–30102

    Article  PubMed  CAS  Google Scholar 

  • Buss H, Dorrie A, Schmitz ML, Hoffmann E, Resch K, Kracht M (2004) Constitutive and interleukin-1-inducible phosphorylation of p65 NF-{kappa}B at serine 536 is mediated by multiple protein kinases including I{kappa}B kinase (IKK)-{alpha}, IKK{beta}, IKK{epsilon}, TRAF family member-associated (TANK)-binding kinase 1 (TBK1), and an unknown kinase and couples p65 to TATA-binding protein-associated factor II31-mediated interleukin-8 transcription. J Biol Chem 279:55633–55643

    Article  PubMed  CAS  Google Scholar 

  • Cao W, Bao C, Padalko E, Lowenstein CJ (2008) Acetylation of mitogen-activated protein kinase phosphatase-1 inhibits Toll-like receptor signaling. J Exp Med 205:1491–1503

    Article  PubMed  CAS  Google Scholar 

  • Chen LF, Mu Y, Greene WC (2002) Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kappaB. EMBO J 21:6539–6548

    Article  PubMed  CAS  Google Scholar 

  • Chen LF, Williams SA, Mu Y, Nakano H, Duerr JM, Buckbinder L, Greene WC (2005) NF-kappaB RelA phosphorylation regulates RelA acetylation. Mol Cell Biol 25:7966–7975

    Article  PubMed  CAS  Google Scholar 

  • Denes A, Thornton P, Rothwell NJ, Allan SM (2010) Inflammation and brain injury: acute cerebral ischaemia, peripheral and central inflammation. Brain Behav Immun 24:708–723

    Article  PubMed  CAS  Google Scholar 

  • Des Rosiers C, David F, Garneau M, Brunengraber H (1991) Nonhomogeneous labeling of liver mitochondrial acetyl-CoA. J Biol Chem 266:1574–1578

    PubMed  CAS  Google Scholar 

  • Deutsch J, Rapoport SI, Rosenberger TA (2002) Coenzyme A and short-chain acyl-CoA species in control and ischemic rat brain. Neurochem Res 27:1577–1582

    Article  PubMed  CAS  Google Scholar 

  • Dhawan G, Floden AM, Combs CK (2012) Amyloid-beta oligomers stimulate microglia through a tyrosine kinase dependent mechanism. Neurobiol Aging 33:2247–2261

    Article  PubMed  CAS  Google Scholar 

  • Dong Y, Benveniste EN (2001) Immune function of astrocytes. Glia 36:180–190

    Article  PubMed  CAS  Google Scholar 

  • Fernandez AM, Fernandez S, Carrero P, Garcia-Garcia M, Torres-Aleman I (2007) Calcineurin in reactive astrocytes plays a key role in the interplay between proinflammatory and anti-inflammatory signals. J Neurosci 27:8745–8756

    Article  PubMed  CAS  Google Scholar 

  • Fujino T, Kondo J, Ishikawa M, Morikawa K, Yamamoto TT (2001) Acetyl-CoA synthetase 2, a mitochondrial matrix enzyme involved in the oxidation of acetate. J Biol Chem 276:11420–11426

    Article  PubMed  CAS  Google Scholar 

  • Fukao T, Lopaschuk GD, Mitchell GA (2004) Pathways and control of ketone body metabolism: on the fringe of lipid biochemistry. Prostag Leukot Essent Fatty Acids 70:243–251

    Article  CAS  Google Scholar 

  • Garcia CK, Li X, Luna J, Francke U (1994a) cDNA cloning of the human monocarboxylate transporter 1 and chromosomal localization of the SLC16A1 locus to 1p13.2-p12. Genomics 23:500–503

    Article  PubMed  CAS  Google Scholar 

  • Garcia CK, Goldstein JL, Pathak RK, Anderson RG, Brown MS (1994b) Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle. Cell 76:865–873

    Article  PubMed  CAS  Google Scholar 

  • Glozak MA, Sengupta N, Zhang X, Seto E (2005) Acetylation and deacetylation of non-histone proteins. Gene 363:15–23

    Article  PubMed  CAS  Google Scholar 

  • Gorina R, Santalucia T, Petegnief V, Ejarque-Ortiz A, Saura J, Planas AM (2009) Astrocytes are very sensitive to develop innate immune responses to lipid-carried short interfering RNA. Glia 57:93–107

    Article  PubMed  Google Scholar 

  • Gorina R, Font-Nieves M, Marquez-Kisinousky L, Santalucia T, Planas AM (2011) Astrocyte TLR4 activation induces a proinflammatory environment through the interplay between MyD88-dependent NFkappaB signaling, MAPK, and Jak1/Stat1 pathways. Glia 59:242–255

    Article  PubMed  Google Scholar 

  • Govindarajan N, Agis-Balboa RC, Walter J, Sananbenesi F, Fischer A (2011) Sodium butyrate improves memory function in an Alzheimer’s disease mouse model when administered at an advanced stage of disease progression. J Alzheim Dis 26:187–197

    CAS  Google Scholar 

  • Hamby ME, Sofroniew MV (2010) Reactive astrocytes as therapeutic targets for CNS disorders. Neurotherapeutics 7:494–506

    Article  PubMed  CAS  Google Scholar 

  • Hanisch UK, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10:1387–1394

    Article  PubMed  CAS  Google Scholar 

  • Helmy A, De Simoni MG, Guilfoyle MR, Carpenter KL, Hutchinson PJ (2011) Cytokines and innate inflammation in the pathogenesis of human traumatic brain injury. Prog Neurobiol 95:352–372

    Article  PubMed  CAS  Google Scholar 

  • Hoberg JE, Popko AE, Ramsey CS, Mayo MW (2006) IkappaB kinase alpha-mediated derepression of SMRT potentiates acetylation of RelA/p65 by p300. Mol Cell Biol 26:457–471

    Article  PubMed  CAS  Google Scholar 

  • Hosoi R, Matsuyama Y, Hirose S, Koyama Y, Matsuda T, Gee A, Inoue O (2009) Characterization of (14)C-acetate uptake in cultured rat astrocytes. Brain Res 1253:69–73

    Article  PubMed  CAS  Google Scholar 

  • Huang B, Yang XD, Lamb A, Chen LF (2010) Posttranslational modifications of NF-kappaB: another layer of regulation for NF-kappaB signaling pathway. Cell Signal 22:1282–1290

    Article  PubMed  CAS  Google Scholar 

  • Imhof A, Yang XJ, Ogryzko VV, Nakatani Y, Wolffe AP, Ge H (1997) Acetylation of general transcription factors by histone acetyltransferases. Curr Biol 7:689–692

    Article  PubMed  CAS  Google Scholar 

  • Ito M, Natsume A, Takeuchi H, Shimato S, Ohno M, Wakabayashi T, Yoshida J (2009) Type I interferon inhibits astrocytic gliosis and promotes functional recovery after spinal cord injury by deactivation of the MEK/ERK pathway. J Neurotrauma 26:41–53

    Article  PubMed  Google Scholar 

  • Johnston H, Boutin H, Allan SM (2011) Assessing the contribution of inflammation in models of Alzheimer’s disease. Biochem Soc Trans 39:886–890

    Article  PubMed  CAS  Google Scholar 

  • Kang W, Hebert JM (2011) Signaling pathways in reactive astrocytes, a genetic perspective. Mol Neurobiol 43:147–154

    Article  PubMed  CAS  Google Scholar 

  • Kasai T, Inada K, Takakuwa T, Yamada Y, Inoue Y, Shimamura T, Taniguchi S, Sato S, Wakabayashi G, Endo S (1997) Anti-inflammatory cytokine levels in patients with septic shock. Res Commun Mol Pathol Pharmacol 98:34–42

    PubMed  CAS  Google Scholar 

  • Kim JH, Min KJ, Seol W, Jou I, Joe EH (2010) Astrocytes in injury states rapidly produce anti-inflammatory factors and attenuate microglial inflammatory responses. J Neurochem 115:1161–1171

    Article  PubMed  CAS  Google Scholar 

  • Ledeboer A, Breve JJ, Poole S, Tilders FJ, Van Dam AM (2000) Interleukin-10, interleukin-4, and transforming growth factor-beta differentially regulate lipopolysaccharide-induced production of pro-inflammatory cytokines and nitric oxide in co-cultures of rat astroglial and microglial cells. Glia 30:134–142

    Article  PubMed  CAS  Google Scholar 

  • Lee S, Zhao YQ, Ribeiro-da-Silva A, Zhang J (2010) Distinctive response of CNS glial cells in oro-facial pain associated with injury, infection and inflammation. Mol Pain 6:79

    Article  PubMed  CAS  Google Scholar 

  • Legos JJ, Erhardt JA, White RF, Lenhard SC, Chandra S, Parsons AA, Tuma RF, Barone FC (2001) SB 239063, a novel p38 inhibitor, attenuates early neuronal injury following ischemia. Brain Res 892:70–77

    Article  PubMed  CAS  Google Scholar 

  • Lehnardt S (2010) Innate immunity and neuroinflammation in the CNS: the role of microglia in Toll-like receptor-mediated neuronal injury. Glia 58:253–263

    PubMed  Google Scholar 

  • Lu X, Ma L, Ruan L, Kong Y, Mou H, Zhang Z, Wang Z, Wang JM, Le Y (2010) Resveratrol differentially modulates inflammatory responses of microglia and astrocytes. J Neuroinflammation 7:46

    Article  PubMed  Google Scholar 

  • Madhavarao CN, Arun P, Anikster Y, Mog SR, Staretz-Chacham O, Moffett JR, Grunberg NE, Gahl WA, Namboodiri AM (2009) Glyceryl triacetate for Canavan disease: a low-dose trial in infants and evaluation of a higher dose for toxicity in the tremor rat model. J Inherit Metab Dis 32:640–650

    Article  PubMed  CAS  Google Scholar 

  • Mathew R, Arun P, Madhavarao CN, Moffett JR, Namboodiri MA (2005) Progress toward acetate supplementation therapy for Canavan disease: glyceryl triacetate administration increases acetate, but not N-acetylaspartate, levels in brain. J Pharmacol Exp Ther 315:297–303

    Article  PubMed  CAS  Google Scholar 

  • McGarry JD, Foster DW (1980) Regulation of hepatic fatty acid oxidation and ketone body production. Annu Rev Biochem 49:395–420

    Article  PubMed  CAS  Google Scholar 

  • Merson TD, Binder MD, Kilpatrick TJ (2010) Role of cytokines as mediators and regulators of microglial activity in inflammatory demyelination of the CNS. Neuromolecular Med 12:99–132

    Article  PubMed  CAS  Google Scholar 

  • Min KJ, Yang MS, Kim SU, Jou I, Joe EH (2006) Astrocytes induce hemeoxygenase-1 expression in microglia: a feasible mechanism for preventing excessive brain inflammation. J Neurosci 26:1880–1887

    Article  PubMed  CAS  Google Scholar 

  • Mori T, Wang X, Aoki T, Lo EH (2002) Downregulation of matrix metalloproteinase-9 and attenuation of edema via inhibition of ERK mitogen activated protein kinase in traumatic brain injury. J Neurotrauma 19:1411–1419

    Article  PubMed  Google Scholar 

  • Muir D, Berl S, Clarke DD (1986) Acetate and fluoroacetate as possible markers for glial metabolism in vivo. Brain Res 380:336–340

    Article  PubMed  CAS  Google Scholar 

  • Munoz C, Carlet J, Fitting C, Misset B, Bleriot JP, Cavaillon JM (1991) Dysregulation of in vitro cytokine production by monocytes during sepsis. J Clin Invest 88:1747–1754

    Article  PubMed  CAS  Google Scholar 

  • Oldendorf WH (1973) Carrier-mediated blood-brain barrier transport of short-chain monocarboxylic organic acids. Am J Physiol 224:1450–1453

    PubMed  CAS  Google Scholar 

  • Olson JK, Miller SD (2004) Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J Immunol 173:3916–3924

    PubMed  CAS  Google Scholar 

  • Pekny M, Nilsson M (2005) Astrocyte activation and reactive gliosis. Glia 50:427–434

    Article  PubMed  Google Scholar 

  • Piao CS, Kim JB, Han PL, Lee JK (2003) Administration of the p38 MAPK inhibitor SB203580 affords brain protection with a wide therapeutic window against focal ischemic insult. J Neurosci Res 73:537–544

    Article  PubMed  CAS  Google Scholar 

  • Pierre K, Pellerin L, Debernardi R, Riederer BM, Magistretti PJ (2000) Cell-specific localization of monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain revealed by double immunohistochemical labeling and confocal microscopy. Neuroscience 100:617–627

    Article  PubMed  CAS  Google Scholar 

  • Polevoda B, Sherman F (2002) The diversity of acetylated proteins. Genome Biol 3:0006.1–0006.6

    Article  Google Scholar 

  • Poli V (1998) The role of C/EBP isoforms in the control of inflammatory and native immunity functions. J Biol Chem 273:29279–29282

    Article  PubMed  CAS  Google Scholar 

  • Poli V, Mancini FP, Cortese R (1990) IL-6DBP, a nuclear protein involved in interleukin-6 signal transduction, defines a new family of leucine zipper proteins related to C/EBP. Cell 63:643–653

    Article  PubMed  CAS  Google Scholar 

  • Qian L, Flood PM, Hong JS (2010) Neuroinflammation is a key player in Parkinson’s disease and a prime target for therapy. J Neural Transm 117:971–979

    Article  PubMed  CAS  Google Scholar 

  • Rafiki A, Boulland JL, Halestrap AP, Ottersen OP, Bergersen L (2003) Highly differential expression of the monocarboxylate transporters MCT2 and MCT4 in the developing rat brain. Neuroscience 122:677–688

    Article  PubMed  CAS  Google Scholar 

  • Ramji DP, Foka P (2002) CCAAT/enhancer-binding proteins: structure, function and regulation. Biochem J 365:561–575

    PubMed  CAS  Google Scholar 

  • Ransohoff RM, Perry VH (2009) Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol 27:119–145

    Article  PubMed  CAS  Google Scholar 

  • Reisenauer CJ, Bhatt DP, Mitteness DJ, Slanczka ER, Gienger HM, Watt JA, Rosenberger TA (2011) Acetate supplementation attenuates lipopolysaccharide-induced neuroinflammation. J Neurochem 117:264–274

    Article  PubMed  CAS  Google Scholar 

  • Rice JC, Allis CD (2001) Histone methylation versus histone acetylation: new insights into epigenetic regulation. Curr Opin Cell Biol 13:263–273

    Article  PubMed  CAS  Google Scholar 

  • Schonthaler HB, Guinea-Viniegra J, Wagner EF (2011) Targeting inflammation by modulating the Jun/AP-1 pathway. Ann Rheum Dis 70(Suppl 1):i109–i112

    Article  PubMed  CAS  Google Scholar 

  • Segel R, Anikster Y, Zevin S, Steinberg A, Gahl WA, Fisher D, Staretz-Chacham O, Zimran A, Altarescu G (2011) A safety trial of high dose glyceryl triacetate for Canavan disease. Mol Genet Metab 103:203–206

    Article  PubMed  CAS  Google Scholar 

  • Shaftel SS, Griffin WS, O'Banion MK (2008) The role of interleukin-1 in neuroinflammation and Alzheimer disease: an evolving perspective. J Neuroinflammation 5:7

    Article  PubMed  Google Scholar 

  • Silva PF, Garcia VA, Dornelles Ada S, Silva VK, Maurmann N, Portal BC, Ferreira RD, Piazza FC, Roesler R, Schroder N (2012) Memory impairment induced by brain iron overload is accompanied by reduced H3K9 acetylation and ameliorated by sodium butyrate. Neuroscience 200:42–49

    Article  PubMed  Google Scholar 

  • Sofroniew MV (2009) Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci 32:638–647

    Article  PubMed  CAS  Google Scholar 

  • Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119:7–35

    Article  PubMed  Google Scholar 

  • Soliman ML, Rosenberger TA (2011) Acetate supplementation increases brain histone acetylation and inhibits histone deacetylase activity and expression. Mol Cell Biochem 352:173–180

    Article  PubMed  CAS  Google Scholar 

  • Soliman ML, Puig KL, Combs CK, Rosenberger TA (2012a) Acetate reduces microglia inflammatory signaling in vitro. J Neurochem 123:555–567

    Article  PubMed  CAS  Google Scholar 

  • Soliman ML, Smith MD, Houdek HM, Rosenberger TA (2012b) Acetate supplementation modulates brain histone acetylation and decreases interleukin-1beta expression in a rat model of neuroinflammation. J Neuroinflammation 9:51

    Article  PubMed  CAS  Google Scholar 

  • Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403:41–45

    Article  PubMed  CAS  Google Scholar 

  • Streit WJ, Walter SA, Pennell NA (1999) Reactive microgliosis. Prog Neurobiol 57:563–581

    Article  PubMed  CAS  Google Scholar 

  • Sugino T, Nozaki K, Takagi Y, Hattori I, Hashimoto N, Moriguchi T, Nishida E (2000) Activation of mitogen-activated protein kinases after transient forebrain ischemia in gerbil hippocampus. J Neurosci 20:4506–4514

    PubMed  CAS  Google Scholar 

  • Tanaka T, Akira S, Yoshida K, Umemoto M, Yoneda Y, Shirafuji N, Fujiwara H, Suematsu S, Yoshida N, Kishimoto T (1995) Targeted disruption of the NF-IL6 gene discloses its essential role in bacteria killing and tumor cytotoxicity by macrophages. Cell 80:353–361

    Article  PubMed  CAS  Google Scholar 

  • Terasaki T (1992) Studies on the mechanism of drug distribution in tissues. Yakugaku Zasshi 112:887–905

    PubMed  CAS  Google Scholar 

  • Thoren AE, Helps SC, Nilsson M, Sims NR (2005) Astrocytic function assessed from 1-14C-acetate metabolism after temporary focal cerebral ischemia in rats. J Cereb Blood Flow Metab 25:440–450

    Article  PubMed  CAS  Google Scholar 

  • Tian L, Ma L, Kaarela T, Li Z (2012) Neuroimmune crosstalk in the central nervous system and its significance for neurological diseases. J Neuroinflammation 9:155

    Article  PubMed  CAS  Google Scholar 

  • Vitkovic L, Maeda S, Sternberg E (2001) Anti-inflammatory cytokines: expression and action in the brain. Neuroimmunomodulation 9:295–312

    Article  PubMed  CAS  Google Scholar 

  • Waniewski RA, Martin DL (1998) Preferential utilization of acetate by astrocytes is attributable to transport. J Neurosci 18:5225–5233

    PubMed  CAS  Google Scholar 

  • Wyss MT, Weber B, Treyer V, Heer S, Pellerin L, Magistretti PJ, Buck A (2009) Stimulation-induced increases of astrocytic oxidative metabolism in rats and humans investigated with 1-11C-acetate. J Cereb Blood Flow Metab 29:44–56

    Article  PubMed  CAS  Google Scholar 

  • Wyss MT, Magistretti PJ, Buck A, Weber B (2011) Labeled acetate as a marker of astrocytic metabolism. J Cereb Blood Flow Metab 31:1668–1674

    Article  PubMed  CAS  Google Scholar 

  • Yang H, Feng GD, Liang Z, Vitale A, Jiao XY, Ju G, You SW (2012) In vitro beneficial activation of microglial cells by mechanically-injured astrocytes enhances the synthesis and secretion of BDNF through p38MAPK. Neurochem Int 61:175–186

    Article  PubMed  CAS  Google Scholar 

  • Zhang B, West EJ, Van KC, Gurkoff GG, Zhou J, Zhang XM, Kozikowski AP, Lyeth BG (2008) HDAC inhibitor increases histone H3 acetylation and reduces microglia inflammatory response following traumatic brain injury in rats. Brain Res 1226:181–191

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This publication was made possible by Grant Number 5P20RR017699 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). We would like to thank Dr. Bhanu Dasari for his assistance in using the confocal microscope in the Edward C. Carlson Image and Image Analysis Core Facility.

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The authors declare that they have no conflict of interest.

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  1. Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Room 3742, Grand Forks, ND, 58203, USA

    Mahmoud L. Soliman, Colin K. Combs & Thad A. Rosenberger

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  1. Mahmoud L. Soliman
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Soliman, M.L., Combs, C.K. & Rosenberger, T.A. Modulation of Inflammatory Cytokines and Mitogen-activated Protein Kinases by Acetate in Primary Astrocytes. J Neuroimmune Pharmacol 8, 287–300 (2013). https://doi.org/10.1007/s11481-012-9426-4

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