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Inflammatory Activation of Microglia and Astrocytes in Manganese Neurotoxicity

  • Ronald B. TjalkensEmail author
  • Katriana A. Popichak
  • Kelly A. Kirkley
Chapter
Part of the Advances in Neurobiology book series (NEUROBIOL, volume 18)

Abstract

Neurotoxicity due to excessive exposure to manganese (Mn) has been described as early as 1837 (Couper, Br Ann Med Pharm Vital Stat Gen Sci 1:41–42, 1837). Extensive research over the past two decades has revealed that Mn-induced neurological injury involves complex pathophysiological signaling mechanisms between neurons and glial cells. Glial cells are an important target of Mn in the brain, both for sequestration of the metal, as well as for activating inflammatory signaling pathways that damage neurons through overproduction of numerous reactive oxygen and nitrogen species and inflammatory cytokines. Understanding how these pathways are regulated in glial cells during Mn exposure is critical to determining the mechanisms underlying permanent neurological dysfunction stemming from excess exposure. The subject of this review will be to delineate mechanisms by which Mn interacts with glial cells to perturb neuronal function, with a particular emphasis on neuroinflammation and neuroinflammatory signaling between distinct populations of glial cells.

Keywords

Manganism Pattern recognition receptors (PRRs) Astrogliosis Glial fibrillary acidic protein (GFAP) Parkinson’s disease (PD) 

References

  1. Alcamo E, et al. Targeted mutation of TNF receptor I rescues the RelA-deficient mouse and reveals a critical role for NF-kappa B in leukocyte recruitment. J Immunol. 2001;167:1592–600.PubMedCrossRefGoogle Scholar
  2. Araque A, Carmignoto G, Haydon PG. Dynamic signaling between astrocytes and neurons. Annu Rev Physiol. 2001;63:795–813. doi: 10.1146/annurev.physiol.63.1.795.PubMedCrossRefGoogle Scholar
  3. Aschner M, Aschner JL. Manganese neurotoxicity: cellular effects and blood-brain barrier transport. Neurosci Biobehav Rev. 1991;15:333–40.PubMedCrossRefGoogle Scholar
  4. Aschner JL, Aschner M. Nutritional aspects of manganese homeostasis. Mol Asp Med. 2005;26:353–62. doi: 10.1016/j.mam.2005.07.003.CrossRefGoogle Scholar
  5. Aschner M, Gannon M, Kimelberg HK. Manganese uptake and efflux in cultured rat astrocytes. J Neurochem. 1992;58:730–5.PubMedCrossRefGoogle Scholar
  6. Barhoumi R, Faske J, Liu X, Tjalkens RB. Manganese potentiates lipopolysaccharide-induced expression of NOS2 in C6 glioma cells through mitochondrial-dependent activation of nuclear factor kappaB. Brain Res Mol Brain Res. 2004;122:167–79. doi: 10.1016/j.molbrainres.2003.12.009.PubMedCrossRefGoogle Scholar
  7. Block ML, Hong JS. Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol. 2005;76:77–98. doi: 10.1016/j.pneurobio.2005.06.004.PubMedCrossRefGoogle Scholar
  8. Bonizzi G, Karin M. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol. 2004;25:280–8. doi: 10.1016/j.it.2004.03.008.PubMedCrossRefGoogle Scholar
  9. Brambilla R, et al. Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury. J Exp Med. 2005;202:145–56. doi: 10.1084/jem.20041918.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Brambilla R, et al. Transgenic inhibition of astroglial NF-kappa B improves functional outcome in experimental autoimmune encephalomyelitis by suppressing chronic central nervous system inflammation. J Immunol. 2009;182:2628–40. doi: 10.4049/jimmunol.0802954.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Carbone DL, Popichak KA, Moreno JA, Safe S, Tjalkens RB. Suppression of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nitric-oxide synthase 2 expression in astrocytes by a novel diindolylmethane analog protects striatal neurons against apoptosis. Mol Pharmacol. 2009;75:35–43. doi: 10.1124/mol.108.050781.PubMedCrossRefGoogle Scholar
  12. Carmignoto G, Gomez-Gonzalo M. The contribution of astrocyte signalling to neurovascular coupling. Brain Res Rev. 2010;63:138–48. doi: 10.1016/j.brainresrev.2009.11.007.PubMedCrossRefGoogle Scholar
  13. Centonze D, Gubellini P, Bernardi G, Calabresi P. Impaired excitatory transmission in the striatum of rats chronically intoxicated with manganese. Exp Neurol. 2001;172:469–76. doi: 10.1006/exnr.2001.7812.PubMedCrossRefGoogle Scholar
  14. Chang JY, Liu LZ. Manganese potentiates nitric oxide production by microglia. Brain Res Mol Brain Res. 1999;68:22–8.PubMedCrossRefGoogle Scholar
  15. Chao CC, Hu S, Molitor TW, Shaskan EG, Peterson PK. Activated microglia mediate neuronal cell injury via a nitric oxide mechanism. J Immunol. 1992;149:2736–41.PubMedGoogle Scholar
  16. Chen CJ, et al. Manganese modulates pro-inflammatory gene expression in activated glia. Neurochem Int. 2006;49:62–71. doi: 10.1016/j.neuint.2005.12.020.PubMedCrossRefGoogle Scholar
  17. Cho IH, et al. Role of microglial IKKbeta in kainic acid-induced hippocampal neuronal cell death. Brain. 2008;131:3019–33. doi: 10.1093/brain/awn230.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Christopherson KS, et al. Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis. Cell. 2005;120:421–33. doi: 10.1016/j.cell.2004.12.020.PubMedCrossRefGoogle Scholar
  19. Collipp PJ, Chen SY, Maitinsky S. Manganese in infant formulas and learning disability. Ann Nutr Metab. 1983;27:488–94.PubMedCrossRefGoogle Scholar
  20. Couper J. On the effects of black oxide of manganese when inhaled into the lungs. British Annals of Medicine, Pharmacy, Vital Statistics, and General Science. 1837;1:41–2.Google Scholar
  21. Craft JM, Watterson DM, Van Eldik LJ. Neuroinflammation: a potential therapeutic target. Expert Opin Ther Targets. 2005;9:887–900. doi: 10.1517/14728222.9.5.887.PubMedCrossRefGoogle Scholar
  22. Crittenden PL, Filipov NM. Manganese modulation of MAPK pathways: effects on upstream mitogen activated protein kinase kinases and mitogen activated kinase phosphatase-1 in microglial cells. J Appl Toxicol. 2011;31:1–10. doi: 10.1002/jat.1552.PubMedPubMedCentralCrossRefGoogle Scholar
  23. David S, Kroner A. Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci. 2011;12:388–99. doi: 10.1038/nrn3053.PubMedCrossRefGoogle Scholar
  24. De Miranda BR, et al. The Nurr1 activator 1,1-Bis(3′-Indolyl)-1-(p-Chlorophenyl)methane blocks inflammatory Gene expression in BV-2 microglial cells by inhibiting nuclear factor kappaB. Mol Pharmacol. 2015a;87:1021–34. doi: 10.1124/mol.114.095398.PubMedPubMedCentralCrossRefGoogle Scholar
  25. De Miranda BR, et al. Novel para-phenyl substituted diindolylmethanes protect against MPTP neurotoxicity and suppress glial activation in a mouse model of Parkinson’s disease. Toxicol Sci. 2015b;143:360–73. doi: 10.1093/toxsci/kfu236.PubMedCrossRefGoogle Scholar
  26. Di Virgilio F, Ceruti S, Bramanti P, Abbracchio MP. Purinergic signalling in inflammation of the central nervous system. Trends Neurosci. 2009;32:79–87. doi: 10.1016/j.tins.2008.11.003.PubMedCrossRefGoogle Scholar
  27. Diaz-Aparicio I, Beccari S, Abiega O, Sierra A. Clearing the corpses: regulatory mechanisms, novel tools, and therapeutic potential of harnessing microglial phagocytosis in the diseased brain. Neural Regen Res. 2016;11:1533–9. doi: 10.4103/1673-5374.193220.PubMedPubMedCentralCrossRefGoogle Scholar
  28. DiDonato JA, Hayakawa M, Rothwarf DM, Zandi E, Karin M. A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB. Nature. 1997;388:548–54. doi: 10.1038/41493.PubMedCrossRefGoogle Scholar
  29. Doetsch F. The glial identity of neural stem cells. Nat Neurosci. 2003;6:1127–34. doi: 10.1038/nn1144.PubMedCrossRefGoogle Scholar
  30. Filipov NM, Dodd CA. Role of glial cells in manganese neurotoxicity. J Appl Toxicol. 2012;32:310–7. doi: 10.1002/jat.1762.PubMedCrossRefGoogle Scholar
  31. Filipov NM, Seegal RF, Lawrence DA. Manganese potentiates in vitro production of proinflammatory cytokines and nitric oxide by microglia through a nuclear factor kappa B-dependent mechanism. Toxicol Sci. 2005;84:139–48. doi: 10.1093/toxsci/kfi055.PubMedCrossRefGoogle Scholar
  32. Frank-Cannon TC, Alto LT, McAlpine FE, Tansey MG. Does neuroinflammation fan the flame in neurodegenerative diseases? Mol Neurodegener. 2009;4:47. doi: 10.1186/1750-1326-4-47.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Gehrmann J, Matsumoto Y, Kreutzberg GW. Microglia: intrinsic immuneffector cell of the brain. Brain Res Brain Res Rev. 1995;20:269–87.PubMedCrossRefGoogle Scholar
  34. Gensel JC, Kigerl KA, Mandrekar-Colucci SS, Gaudet AD, Popovich PG. Achieving CNS axon regeneration by manipulating convergent neuro-immune signaling. Cell Tissue Res. 2012;349:201–13. doi: 10.1007/s00441-012-1425-5.PubMedCrossRefGoogle Scholar
  35. Giordano G, Pizzurro D, VanDeMark K, Guizzetti M, Costa LG. Manganese inhibits the ability of astrocytes to promote neuronal differentiation. Toxicol Appl Pharmacol. 2009;240:226–35. doi: 10.1016/j.taap.2009.06.004.PubMedCrossRefGoogle Scholar
  36. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell. 2010;140:918–34. doi: 10.1016/j.cell.2010.02.016.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Gonzalez-Scarano F, Baltuch G. Microglia as mediators of inflammatory and degenerative diseases. Annu Rev Neurosci. 1999;22:219–40. doi: 10.1146/annurev.neuro.22.1.219.PubMedCrossRefGoogle Scholar
  38. Guilarte TR. Manganese and Parkinson’s disease: a critical review and new findings. Environ Health Perspect. 2010;118:1071–80. doi: 10.1289/ehp.0901748.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Hamby ME, Hewett JA, Hewett SJ. TGF-beta1 potentiates astrocytic nitric oxide production by expanding the population of astrocytes that express NOS-2. Glia. 2006;54:566–77. doi: 10.1002/glia.20411.PubMedCrossRefGoogle Scholar
  40. Harischandra DS, Jin H, Anantharam V, Kanthasamy A, Kanthasamy AG. Alpha-Synuclein protects against manganese neurotoxic insult during the early stages of exposure in a dopaminergic cell model of Parkinson’s disease. Toxicol Sci. 2015;143:454–68. doi: 10.1093/toxsci/kfu247.PubMedCrossRefGoogle Scholar
  41. Hirsch EC, Hunot S. Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol. 2009;8:382–97. doi: 10.1016/S1474-4422(09)70062-6.PubMedCrossRefGoogle Scholar
  42. Hua MS, Huang CC. Chronic occupational exposure to manganese and neurobehavioral function. J Clin Exp Neuropsychol. 1991;13:495–507. doi: 10.1080/01688639108401066.PubMedCrossRefGoogle Scholar
  43. Husemann J, Loike JD, Anankov R, Febbraio M, Silverstein SC. Scavenger receptors in neurobiology and neuropathology: their role on microglia and other cells of the nervous system. Glia. 2002;40:195–205. doi: 10.1002/glia.10148.PubMedCrossRefGoogle Scholar
  44. Karin M. How NF-kappaB is activated: the role of the IkappaB kinase (IKK) complex. Oncogene. 1999;18:6867–74. doi: 10.1038/sj.onc.1203219.PubMedCrossRefGoogle Scholar
  45. Karin M. Inflammation-activated protein kinases as targets for drug development. Proc Am Thorac Soc. 2005;2:386–390.; discussion 394–385. doi: 10.1513/pats.200504-034SR.PubMedPubMedCentralCrossRefGoogle Scholar
  46. Kaushal V, Schlichter LC. Mechanisms of microglia-mediated neurotoxicity in a new model of the stroke penumbra. J Neurosci. 2008;28:2221–30. doi: 10.1523/JNEUROSCI.5643-07.2008.PubMedCrossRefGoogle Scholar
  47. Kigerl KA, et al. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci. 2009;29:13435–44. doi: 10.1523/JNEUROSCI.3257-09.2009.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Kim SU, de Vellis J. Microglia in health and disease. J Neurosci Res. 2005;81:302–13. doi: 10.1002/jnr.20562.PubMedCrossRefGoogle Scholar
  49. Kim YS, et al. Matrix metalloproteinase-3: a novel signaling proteinase from apoptotic neuronal cells that activates microglia. J Neurosci. 2005;25:3701–11. doi: 10.1523/JNEUROSCI.4346-04.2005.PubMedCrossRefGoogle Scholar
  50. Kim Y, et al. Co-exposure to environmental lead and manganese affects the intelligence of school-aged children. Neurotoxicology. 2009;30:564–71. doi: 10.1016/j.neuro.2009.03.012.PubMedCrossRefGoogle Scholar
  51. Kimelberg HK. The problem of astrocyte identity. Neurochem Int. 2004;45:191–202. doi: 10.1016/j.neuint.2003.08.015.PubMedCrossRefGoogle Scholar
  52. Kuno R, et al. The role of TNF-alpha and its receptors in the production of NGF and GDNF by astrocytes. Brain Res. 2006;1116:12–8. doi: 10.1016/j.brainres.2006.07.120.PubMedCrossRefGoogle Scholar
  53. Lalo U, et al. P2X1 and P2X5 subunits form the functional P2X receptor in mouse cortical astrocytes. J Neurosci. 2008;28:5473–80. doi: 10.1523/JNEUROSCI.1149-08.2008.PubMedPubMedCentralCrossRefGoogle Scholar
  54. Lawson LJ, Perry VH, Dri P, Gordon S. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience. 1990;39:151–70.PubMedCrossRefGoogle Scholar
  55. Lee SC, Liu W, Dickson DW, Brosnan CF, Berman JW. Cytokine production by human fetal microglia and astrocytes. Differential induction by lipopolysaccharide and IL-1 beta. J Immunol. 1993;150:2659–67.PubMedGoogle Scholar
  56. Lee DJ, Hsu MS, Seldin MM, Arellano JL, Binder DK. Decreased expression of the glial water channel aquaporin-4 in the intrahippocampal kainic acid model of epileptogenesis. Exp Neurol. 2012;235:246–55. doi: 10.1016/j.expneurol.2012.02.002.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Li ZW, Omori SA, Labuda T, Karin M, Rickert RC. IKK beta is required for peripheral B cell survival and proliferation. J Immunol. 2003;170:4630–7.PubMedCrossRefGoogle Scholar
  58. Liu B, Gao HM, Hong JS. Parkinson’s disease and exposure to infectious agents and pesticides and the occurrence of brain injuries: role of neuroinflammation. Environ Health Perspect. 2003;111:1065–73.PubMedPubMedCentralCrossRefGoogle Scholar
  59. Liu X, Sullivan KA, Madl JE, Legare M, Tjalkens RB. Manganese-induced neurotoxicity: the role of astroglial-derived nitric oxide in striatal interneuron degeneration. Toxicol Sci. 2006;91:521–31. doi: 10.1093/toxsci/kfj150.PubMedCrossRefGoogle Scholar
  60. Mastroeni D, et al. Microglial responses to dopamine in a cell culture model of Parkinson’s disease. Neurobiol Aging. 2009;30:1805–17. doi: 10.1016/j.neurobiolaging.2008.01.001.PubMedCrossRefGoogle Scholar
  61. Matyash V, Kettenmann H. Heterogeneity in astrocyte morphology and physiology. Brain Res Rev. 2010;63:2–10. doi: 10.1016/j.brainresrev.2009.12.001.PubMedCrossRefGoogle Scholar
  62. McCarty MF. Down-regulation of microglial activation may represent a practical strategy for combating neurodegenerative disorders. Med Hypotheses. 2006;67:251–69. doi: 10.1016/j.mehy.2006.01.013.PubMedCrossRefGoogle Scholar
  63. Menezes-Filho JA, Novaes Cde O, Moreira JC, Sarcinelli PN, Mergler D. Elevated manganese and cognitive performance in school-aged children and their mothers. Environ Res. 2011;111:156–63. doi: 10.1016/j.envres.2010.09.006.PubMedCrossRefGoogle Scholar
  64. Morello M, et al. Sub-cellular localization of manganese in the basal ganglia of normal and manganese-treated rats an electron spectroscopy imaging and electron energy-loss spectroscopy study. Neurotoxicology. 2008;29:60–72. doi: 10.1016/j.neuro.2007.09.001.PubMedCrossRefGoogle Scholar
  65. Moreno JA, Sullivan KA, Carbone DL, Hanneman WH, Tjalkens RB. Manganese potentiates nuclear factor-kappaB-dependent expression of nitric oxide synthase 2 in astrocytes by activating soluble guanylate cyclase and extracellular responsive kinase signaling pathways. J Neurosci Res. 2008;86:2028–38. doi: 10.1002/jnr.21640.PubMedPubMedCentralCrossRefGoogle Scholar
  66. Moreno JA, Streifel KM, Sullivan KA, Legare ME, Tjalkens RB. Developmental exposure to manganese increases adult susceptibility to inflammatory activation of glia and neuronal protein nitration. Toxicol Sci. 2009;112:405–15. doi: 10.1093/toxsci/kfp221.PubMedPubMedCentralCrossRefGoogle Scholar
  67. Moreno JA, Streifel KM, Sullivan KA, Hanneman WH, Tjalkens RB. Manganese-induced NF-kappaB activation and nitrosative stress is decreased by estrogen in juvenile mice. Toxicol Sci. 2011;122:121–33. doi: 10.1093/toxsci/kfr091.PubMedPubMedCentralCrossRefGoogle Scholar
  68. Mosley RL, et al. Neuroinflammation, Oxidative Stress and the Pathogenesis of Parkinson’s Disease. Clin Neurosci Res. 2006;6:261–81. doi: 10.1016/j.cnr.2006.09.006.PubMedPubMedCentralCrossRefGoogle Scholar
  69. Mulligan SJ, MacVicar BA. Calcium transients in astrocyte endfeet cause cerebrovascular constrictions. Nature. 2004;431:195–9. doi: 10.1038/nature02827.PubMedCrossRefGoogle Scholar
  70. Nakajima K, Kohsaka S. Functional roles of microglia in the brain. Neurosci Res. 1993;17:187–203.PubMedCrossRefGoogle Scholar
  71. Neal AP, Guilarte TR. Mechanisms of heavy metal neurotoxicity: lead and manganese. Drug Metab toxicol. 2012;5Google Scholar
  72. Nedergaard M, Verkhratsky A. Artifact versus reality--how astrocytes contribute to synaptic events. Glia. 2012;60:1013–23. doi: 10.1002/glia.22288.PubMedPubMedCentralCrossRefGoogle Scholar
  73. Neher JJ, et al. Inhibition of microglial phagocytosis is sufficient to prevent inflammatory neuronal death. J Immunol. 2011;186:4973–83. doi: 10.4049/jimmunol.1003600.PubMedCrossRefGoogle Scholar
  74. Nimmerjahn A. Astrocytes going live: advances and challenges. J Physiol. 2009;587:1639–47. doi: 10.1113/jphysiol.2008.167171.PubMedPubMedCentralCrossRefGoogle Scholar
  75. O’Callaghan JP, Sriram K. Glial fibrillary acidic protein and related glial proteins as biomarkers of neurotoxicity. Expert Opin Drug Saf. 2005;4:433–42. doi: 10.1517/14740338.4.3.433.PubMedCrossRefGoogle Scholar
  76. Olanow CW. Manganese-induced parkinsonism and Parkinson’s disease. Ann N Y Acad Sci. 2004;1012:209–23.PubMedCrossRefGoogle Scholar
  77. Park E, Chun HS. Melatonin attenuates manganese and lipopolysaccharide-induced inflammatory activation of BV2 microglia. Neurochem Res. 2016; doi: 10.1007/s11064-016-2122-7.
  78. Parpura V, et al. Glial cells in (patho)physiology. J Neurochem. 2012;121:4–27. doi: 10.1111/j.1471-4159.2012.07664.x.PubMedPubMedCentralCrossRefGoogle Scholar
  79. Perea G, Araque A. GLIA modulates synaptic transmission. Brain Res Rev. 2010;63:93–102. doi: 10.1016/j.brainresrev.2009.10.005.PubMedCrossRefGoogle Scholar
  80. Perea G, Navarrete M, Araque A. Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci. 2009;32:421–31. doi: 10.1016/j.tins.2009.05.001.PubMedCrossRefGoogle Scholar
  81. Perl DP, Olanow CW. The neuropathology of manganese-induced parkinsonism. J Neuropathol Exp Neurol. 2007;66:675–82. doi: 10.1097/nen.0b013e31812503cf.PubMedCrossRefGoogle Scholar
  82. Powell EM, Geller HM. Dissection of astrocyte-mediated cues in neuronal guidance and process extension. Glia. 1999;26:73–83.PubMedCrossRefGoogle Scholar
  83. Ransohoff RM, Perry VH. Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol. 2009;27:119–45. doi: 10.1146/annurev.immunol.021908.132528.PubMedCrossRefGoogle Scholar
  84. Riojas-Rodriguez H, et al. Intellectual function in Mexican children living in a mining area and environmentally exposed to manganese. Environ Health Perspect. 2010;118:1465–70.PubMedPubMedCentralCrossRefGoogle Scholar
  85. Saijo K, et al. A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell. 2009;137:47–59. doi: 10.1016/j.cell.2009.01.038.PubMedPubMedCentralCrossRefGoogle Scholar
  86. Santamaria AB. Manganese exposure, essentiality & toxicity. Indian J Med Res. 2008;128:484–500.PubMedGoogle Scholar
  87. Sidoryk-Wegrzynowicz M, Aschner M. Role of astrocytes in manganese mediated neurotoxicity. BMC Pharmacol Toxicol. 2013;14:23. doi: 10.1186/2050-6511-14-23.PubMedPubMedCentralCrossRefGoogle Scholar
  88. Sigel, A. S., H.; Sigel, R.K.O. Metal Ions in Life Sciences. (Wiley, 2007).Google Scholar
  89. Silver J, Miller JH. Regeneration beyond the glial scar. Nat Rev Neurosci. 2004;5:146–56. doi: 10.1038/nrn1326.PubMedCrossRefGoogle Scholar
  90. Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropathol. 2010;119:7–35. doi: 10.1007/s00401-009-0619-8.PubMedCrossRefGoogle Scholar
  91. Spranger M, et al. Manganese augments nitric oxide synthesis in murine astrocytes: a new pathogenetic mechanism in manganism? Exp Neurol. 1998;149:277–83. doi: 10.1006/exnr.1997.6666.PubMedCrossRefGoogle Scholar
  92. Streifel KM, Moreno JA, Hanneman WH, Legare ME, Tjalkens RB. Gene deletion of nos2 protects against manganese-induced neurological dysfunction in juvenile mice. Toxicol Sci. 2012;126:183–92. doi: 10.1093/toxsci/kfr335.PubMedCrossRefGoogle Scholar
  93. Streifel KM, Miller J, Mouneimne R, Tjalkens RB. Manganese inhibits ATP-induced calcium entry through the transient receptor potential channel TRPC3 in astrocytes. Neurotoxicology. 2013;34:160–6. doi: 10.1016/j.neuro.2012.10.014.PubMedCrossRefGoogle Scholar
  94. Streifel KM, et al. Dopaminergic neurotoxicants cause biphasic inhibition of purinergic calcium signaling in astrocytes. PLoS One. 2014;9:e110996. doi: 10.1371/journal.pone.0110996.PubMedPubMedCentralCrossRefGoogle Scholar
  95. Streit WJ. Microglia as neuroprotective, immunocompetent cells of the CNS. Glia. 2002;40:133–9. doi: 10.1002/glia.10154.PubMedCrossRefGoogle Scholar
  96. Suarez-Fernandez MB, et al. Aluminum-induced degeneration of astrocytes occurs via apoptosis and results in neuronal death. Brain Res. 1999;835:125–36.PubMedCrossRefGoogle Scholar
  97. Surprenant A, North RA. Signaling at purinergic P2X receptors. Annu Rev Physiol. 2009;71:333–59. doi: 10.1146/annurev.physiol.70.113006.100630.PubMedCrossRefGoogle Scholar
  98. Takano T, Oberheim N, Cotrina ML, Nedergaard M. Astrocytes and ischemic injury. Stroke. 2009;40:S8–12. doi: 10.1161/STROKEAHA.108.533166.PubMedCrossRefGoogle Scholar
  99. Tansey MG, McCoy MK, Frank-Cannon TC. Neuroinflammatory mechanisms in Parkinson’s disease: potential environmental triggers, pathways, and targets for early therapeutic intervention. Exp Neurol. 2007;208:1–25. doi: 10.1016/j.expneurol.2007.07.004.PubMedPubMedCentralCrossRefGoogle Scholar
  100. Tjalkens RB, Zoran MJ, Mohl B, Barhoumi R. Manganese suppresses ATP-dependent intercellular calcium waves in astrocyte networks through alteration of mitochondrial and endoplasmic reticulum calcium dynamics. Brain Res. 2006;1113:210–9. doi: 10.1016/j.brainres.2006.07.053.PubMedCrossRefGoogle Scholar
  101. van Loo G, et al. Inhibition of transcription factor NF-kappaB in the central nervous system ameliorates autoimmune encephalomyelitis in mice. Nat Immunol. 2006;7:954–61. doi: 10.1038/ni1372.PubMedCrossRefGoogle Scholar
  102. Verina T, Kiihl SF, Schneider JS, Guilarte TR. Manganese exposure induces microglia activation and dystrophy in the substantia nigra of non-human primates. Neurotoxicology. 2011;32:215–26. doi: 10.1016/j.neuro.2010.11.003.PubMedCrossRefGoogle Scholar
  103. Verkhratski AN, Butt A. Glial physiology and pathophysiology. Chichester: Wiley-Blackwell; 2013.CrossRefGoogle Scholar
  104. Verkhratsky A, Steardo L, Parpura V, Montana V. Translational potential of astrocytes in brain disorders. Prog Neurobiol. 2016;144:188–205. doi: 10.1016/j.pneurobio.2015.09.003.PubMedCrossRefGoogle Scholar
  105. Vezzani A, Aronica E, Mazarati A, Pittman QJ. Epilepsy and brain inflammation. Exp Neurol. 2013;244:11–21. doi: 10.1016/j.expneurol.2011.09.033.PubMedCrossRefGoogle Scholar
  106. Webster CM, et al. Microglial P2Y12 deficiency/inhibition protects against brain ischemia. PLoS One. 2013;8:e70927. doi: 10.1371/journal.pone.0070927.PubMedPubMedCentralCrossRefGoogle Scholar
  107. Woolf A, Wright R, Amarasiriwardena C, Bellinger D. A child with chronic manganese exposure from drinking water. Environ Health Perspect. 2002;110:613–6.PubMedPubMedCentralCrossRefGoogle Scholar
  108. Wyss-Coray T, Mucke L. Inflammation in neurodegenerative disease--a double-edged sword. Neuron. 2002;35:419–32.PubMedCrossRefGoogle Scholar
  109. Xu B, Xu ZF, Deng Y. Protective effects of MK-801 on manganese-induced glutamate metabolism disorder in rat striatum. Exp Toxicol Pathol. 2010;62:381–90. doi: 10.1016/j.etp.2009.05.007.PubMedCrossRefGoogle Scholar
  110. Yin Z, et al. Methylmercury induces oxidative injury, alterations in permeability and glutamine transport in cultured astrocytes. Brain Res. 2007;1131:1–10. doi: 10.1016/j.brainres.2006.10.070.PubMedCrossRefGoogle Scholar
  111. Zhang S, Zhou Z, Fu J. Effect of manganese chloride exposure on liver and brain mitochondria function in rats. Environ Res. 2003;93:149–57.PubMedCrossRefGoogle Scholar
  112. Zhang W, et al. Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson’s disease. FASEB J. 2005;19:533–42. doi: 10.1096/fj.04-2751com.PubMedCrossRefGoogle Scholar
  113. Zhang P, et al. Microglia enhance manganese chloride-induced dopaminergic neurodegeneration: role of free radical generation. Exp Neurol. 2009;217:219–30. doi: 10.1016/j.expneurol.2009.02.013.PubMedPubMedCentralCrossRefGoogle Scholar
  114. Zhang P, Lokuta KM, Turner DE, Liu B. Synergistic dopaminergic neurotoxicity of manganese and lipopolysaccharide: differential involvement of microglia and astroglia. J Neurochem. 2010;112:434–43. doi: 10.1111/j.1471-4159.2009.06477.x.PubMedCrossRefGoogle Scholar
  115. Zhao F, et al. Manganese induces dopaminergic neurodegeneration via microglial activation in a rat model of manganism. Toxicol Sci. 2009;107:156–64. doi: 10.1093/toxsci/kfn213.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Ronald B. Tjalkens
    • 1
    • 2
    • 3
    Email author
  • Katriana A. Popichak
    • 1
  • Kelly A. Kirkley
    • 2
    • 3
  1. 1.Program in Cell and Molecular BiologyColorado State UniversityFort CollinsUSA
  2. 2.Center for Environmental MedicineColorado State UniversityFort CollinsUSA
  3. 3.Department of Environmental and Radiological Health SciencesColorado State UniversityFort CollinsUSA

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