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Microglia: The Bodyguard and the Hunter of the Adult Neurogenic Niche

  • Jorge Valero
  • Maria Francisca Eiriz
  • Tiago Santos
  • Ismael Neiva
  • Raquel Ferreira
  • João O. MalvaEmail author
Chapter
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)

Abstract

The addition of new neurons in the mature central nervous system (CNS), which relies on millions of fine-tuned connections, is coordinated by a complex cascade of events. A minimum error could disturb the whole system. All this becomes even more complicated considering that neuroblasts can also move from their place of birth and cover long distances. In this scenario, the most insignificant process should be under the strictest control and any insurgency must be punished with death. For such purposes, microglia seem to be devoted to maintain things in correct order in the brain and to “use the force” when needed. However, on the special environment established in the adult neurogenic niches microglia should be more permissive but also be ready to react when needed. In this chapter, we analyze the particularities of microglial cells on charge of the surveillance of adult neurogenic niches and the tools they have to maintain homeostasis. We comment on the current knowledge about the relationship between microglial cells and other elements of the neurogenic niche during healthy but also inflammatory situations. The activity of senescent and overreactive microglia seems to underlay most of the problems observed in neurodegenerative disorders. Therefore, we consider that an adequate understanding of microglial interaction with the neurogenic niche is essential for the proper development of brain repair therapies.

Keywords

Experimental Autoimmune Encephalomyelitis Status Epilepticus Microglial Cell Olfactory Bulb Middle Cerebral Artery Occlusion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Our work has been supported by Fundação para a Ciência e a Tecnologia (FCT). MFE is part of the MIT-Portugal PhD Program, focused in Bioengineering.

References

  1. 1.
    Alliot F, Godin I, Pessac B (1999) Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res Dev Brain Res 117(2):145–152PubMedCrossRefGoogle Scholar
  2. 2.
    Guillemin GJ, Brew BJ (2004) Microglia, macrophages, perivascular macrophages, and pericytes: a review of function and identification. J Leukoc Biol 75(3):388–397PubMedCrossRefGoogle Scholar
  3. 3.
    Walter L, Neumann H (2009) Role of microglia in neuronal degeneration and regeneration. Semin Immunopathol 31(4):513–525PubMedCrossRefGoogle Scholar
  4. 4.
    Castellano F, Chavrier P, Caron E (2001) Actin dynamics during phagocytosis. Semin Immunol 13(6):347–355PubMedCrossRefGoogle Scholar
  5. 5.
    Myers KR, Casanova JE (2008) Regulation of actin cytoskeleton dynamics by Arf-family GTPases. Trends Cell Biol 18(4):184–192PubMedCrossRefGoogle Scholar
  6. 6.
    Tricker E, Cheng G (2008) With a little help from my friends: modulation of phagocytosis through TLR activation. Cell Res 18(7):711–712PubMedCrossRefGoogle Scholar
  7. 7.
    Koizumi S, Shigemoto-Mogami Y, Nasu-Tada K, Shinozaki Y, Ohsawa K, Tsuda M, Joshi BV, Jacobson KA, Kohsaka S, Inoue K (2007) UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature 446(7139):1091–1095PubMedCrossRefGoogle Scholar
  8. 8.
    Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8(6):752–758PubMedCrossRefGoogle Scholar
  9. 9.
    Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308(5726):1314–1318PubMedCrossRefGoogle Scholar
  10. 10.
    Biber K, Neumann H, Inoue K, Boddeke HW (2007) Neuronal ‘On’ and ‘Off’ signals control microglia. Trends Neurosci 30(11):596–602PubMedCrossRefGoogle Scholar
  11. 11.
    Garden GA, Moller T (2006) Microglia biology in health and disease. J Neuroimmune Pharmacol 1(2):127–137PubMedCrossRefGoogle Scholar
  12. 12.
    Graeber MB, Streit WJ (2010) Microglia: biology and pathology. Acta Neuropathol 119(1):89–105PubMedCrossRefGoogle Scholar
  13. 13.
    Danton GH, Dietrich WD (2003) Inflammatory mechanisms after ischemia and stroke. J Neuropathol Exp Neurol 62(2):127–136PubMedGoogle Scholar
  14. 14.
    Choi J, Koh S (2008) Role of brain inflammation in epileptogenesis. Yonsei Med J 49(1):1–18PubMedCrossRefGoogle Scholar
  15. 15.
    Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8(1):57–69PubMedCrossRefGoogle Scholar
  16. 16.
    Forstreuter F, Lucius R, Mentlein R (2002) Vascular endothelial growth factor induces chemotaxis and proliferation of microglial cells. J Neuroimmunol 132(1–2):93–98PubMedCrossRefGoogle Scholar
  17. 17.
    Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11(5):373–384PubMedCrossRefGoogle Scholar
  18. 18.
    Czeh M, Gressens P, Kaindl AM (2011) The yin and yang of microglia. Dev Neurosci 33(3–4):199–209PubMedCrossRefGoogle Scholar
  19. 19.
    Chavarria A, Alcocer-Varela J (2004) Is damage in central nervous system due to inflammation? Autoimmun Rev 3(4):251–260PubMedCrossRefGoogle Scholar
  20. 20.
    Turrin NP, Rivest S (2006) Molecular and cellular immune mediators of neuroprotection. Mol Neurobiol 34(3):221–242PubMedCrossRefGoogle Scholar
  21. 21.
    Olah M, Biber K, Vinet J, Boddeke HW (2011) Microglia phenotype diversity. CNS Neurol Disord Drug Targets 10(1):108–118PubMedCrossRefGoogle Scholar
  22. 22.
    Pont-Lezica L, Bechade C, Belarif-Cantaut Y, Pascual O, Bessis A (2011) Physiological roles of microglia during development. J Neurochem 119(5):901–908Google Scholar
  23. 23.
    Wakselman S, Bechade C, Roumier A, Bernard D, Triller A, Bessis A (2008) Developmental neuronal death in hippocampus requires the microglial CD11b integrin and DAP12 immunoreceptor. J Neurosci 28(32):8138–8143PubMedCrossRefGoogle Scholar
  24. 24.
    Bessis A, Bechade C, Bernard D, Roumier A (2007) Microglial control of neuronal death and synaptic properties. Glia 55(3):233–238PubMedCrossRefGoogle Scholar
  25. 25.
    Fantin A, Vieira JM, Gestri G, Denti L, Schwarz Q, Prykhozhij S, Peri F, Wilson SW, Ruhrberg C (2010) Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood 116(5):829–840PubMedCrossRefGoogle Scholar
  26. 26.
    Rymo SF, Gerhardt H, Wolfhagen SF, Lang R, Uv A, Betsholtz C (2011) A two-way communication between microglial cells and angiogenic sprouts regulates angiogenesis in aortic ring cultures. PLoS One. 6(1):e15846PubMedCrossRefGoogle Scholar
  27. 27.
    Tremblay ME, Majewska AK (2011) A role for microglia in synaptic plasticity? Commun Integr Biol 4(2):220–222PubMedCrossRefGoogle Scholar
  28. 28.
    Altman J (1969) Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J Comp Neurol 137(4):433–457PubMedCrossRefGoogle Scholar
  29. 29.
    Quinones-Hinojosa A, Sanai N, Soriano-Navarro M, Gonzalez-Perez O, Mirzadeh Z, Gil-Perotin S, Romero-Rodriguez R, Berger MS, Garcia-Verdugo JM, Alvarez-Buylla A (2006) Cellular composition and cytoarchitecture of the adult human subventricular zone: a niche of neural stem cells. J Comp Neurol 494(3):415–434PubMedCrossRefGoogle Scholar
  30. 30.
    Doetsch F, García-Verdugo JM, Álvarez-Buylla A (1997) Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci 17(13):5046–5061PubMedGoogle Scholar
  31. 31.
    Curtis MA, Kam M, Nannmark U, Anderson MF, Axell MZ, Wikkelso C, Holtas S, van Roon-Mom WM, Bjork-Eriksson T, Nordborg C, Frisen J, Dragunow M, Faull RL, Eriksson PS (2007) Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 315(5816):1243–1249PubMedCrossRefGoogle Scholar
  32. 32.
    Altman J, Das GD (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124(3):319–335PubMedCrossRefGoogle Scholar
  33. 33.
    van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH (2002) Functional neurogenesis in the adult hippocampus. Nature 415(6875):1030–1034PubMedCrossRefGoogle Scholar
  34. 34.
    Eriksson PS, Perfilieva E, Björk E, Alborn AM, Nordborg C, Peterson DA, Gage FH (1998) Neurogenesis in the adult human hippocampus. Nat Med 4(11):1313–1317PubMedCrossRefGoogle Scholar
  35. 35.
    Weiss S, Reynolds BA, Vescovi AL, Morshead C, Craig CG, van der Kooy D (1996) Is there a neural stem cell in the mammalian forebrain? Trends Neurosci 19(9):387–393PubMedCrossRefGoogle Scholar
  36. 36.
    Bonaguidi MA, Wheeler MA, Shapiro JS, Stadel RP, Sun GJ, Ming GL, Song H (2011) In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics. Cell 145(7):1142–1155PubMedCrossRefGoogle Scholar
  37. 37.
    Doetsch F, Caille I, Lim DA, García-Verdugo JM, Álvarez-Buylla A (1999) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97(6):703–716PubMedCrossRefGoogle Scholar
  38. 38.
    Morshead CM, van der Kooy D (2004) Disguising adult neural stem cells. Curr Opin Neurobiol 14(1):125–131PubMedCrossRefGoogle Scholar
  39. 39.
    Chiasson BJ, Tropepe V, Morshead CM, van der Kooy D (1999) Adult mammalian forebrain ependymal and subependymal cells demonstrate proliferative potential, but only subependymal cells have neural stem cell characteristics. J Neurosci 19(11):4462–4471PubMedGoogle Scholar
  40. 40.
    Aimone JB, Wiles J, Gage FH (2009) Computational influence of adult neurogenesis on memory encoding. Neuron 61(2):187–202PubMedCrossRefGoogle Scholar
  41. 41.
    Breton-Provencher V, Lemasson M, Peralta MR III, Saghatelyan A (2009) Interneurons produced in adulthood are required for the normal functioning of the olfactory bulb network and for the execution of selected olfactory behaviors. J Neurosci 29(48):15245–15257PubMedCrossRefGoogle Scholar
  42. 42.
    Eisch AJ, Cameron HA, Encinas JM, Meltzer LA, Ming GL, Overstreet-Wadiche LS (2008) Adult neurogenesis, mental health, and mental illness: hope or hype? J Neurosci 28(46):11785–11791PubMedCrossRefGoogle Scholar
  43. 43.
    Lois C, García-Verdugo JM, Álvarez-Buylla A (1996) Chain migration of neuronal precursors. Science 271(5251):978–981PubMedCrossRefGoogle Scholar
  44. 44.
    Bonfanti L, Peretto P, Merighi A, Fasolo A (1997) Newly-generated cells from the rostral migratory stream in the accessory olfactory bulb of the adult rat. Neuroscience 81(2):489–502PubMedCrossRefGoogle Scholar
  45. 45.
    Rochefort C, Gheusi G, Vincent JD, Lledo PM (2002) Enriched odor exposure increases the number of newborn neurons in the adult olfactory bulb and improves odor memory. J Neurosci 22(7):2679–2689PubMedGoogle Scholar
  46. 46.
    Oboti L, Schellino R, Giachino C, Chamero P, Pyrski M, Leinders-Zufall T, Zufall F, Fasolo A, Peretto P (2011) Newborn interneurons in the accessory olfactory bulb promote mate recognition in female mice. Front Neurosci 5:113PubMedCrossRefGoogle Scholar
  47. 47.
    Lagace DC, Whitman MC, Noonan MA, Ables JL, DeCarolis NA, Arguello AA, Donovan MH, Fischer SJ, Farnbauch LA, Beech RD, DiLeone RJ, Greer CA, Mandyam CD, Eisch AJ (2007) Dynamic contribution of nestin-expressing stem cells to adult neurogenesis. J Neurosci 27(46):12623–12629PubMedCrossRefGoogle Scholar
  48. 48.
    Platel JC, Gordon V, Heintz T, Bordey A (2009) GFAP-GFP neural progenitors are antigenically homogeneous and anchored in their enclosed mosaic niche. Glia 57(1):66–78PubMedCrossRefGoogle Scholar
  49. 49.
    Mirzadeh Z, Merkle FT, Soriano-Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A (2008) Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell Stem Cell 3(3):265–278PubMedCrossRefGoogle Scholar
  50. 50.
    Shen Q, Wang Y, Kokovay E, Lin G, Chuang SM, Goderie SK, Roysam B, Temple S (2008) Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell–cell interactions. Cell Stem Cell 3(3):289–300PubMedCrossRefGoogle Scholar
  51. 51.
    Tavazoie M, Van der Veken L, Silva-Vargas V, Louissaint M, Colonna L, Zaidi B, Garcia-Verdugo JM, Doetsch F (2008) A specialized vascular niche for adult neural stem cells. Cell Stem Cell 3(3):279–288Google Scholar
  52. 52.
    Kerever A, Schnack J, Vellinga D, Ichikawa N, Moon C, Arikawa-Hirasawa E, Efird JT, Mercier F (2007) Novel extracellular matrix structures in the neural stem cell niche capture the neurogenic factor fibroblast growth factor 2 from the extracellular milieu. Stem Cells 25(9):2146–2157PubMedCrossRefGoogle Scholar
  53. 53.
    Whitman MC, Fan W, Rela L, Rodriguez-Gil DJ, Greer CA (2009) Blood vessels form a migratory scaffold in the rostral migratory stream. J Comp Neurol 516(2):94–104PubMedCrossRefGoogle Scholar
  54. 54.
    Lois C, Álvarez-Buylla A (1994) Long-distance neuronal migration in the adult mammalian brain. Science 264(5162):1145–1148PubMedCrossRefGoogle Scholar
  55. 55.
    Jankovski A, Sotelo C (1996) Subventricular zone-olfactory bulb migratory pathway in the adult mouse: cellular composition and specificity as determined by heterochronic and heterotopic transplantation. J Comp Neurol 371(3):376–396PubMedCrossRefGoogle Scholar
  56. 56.
    Valero J, Weruaga E, Murias AR, Recio JS, Curto GG, Gomez C, Alonso JR (2007) Changes in cell migration and survival in the olfactory bulb of the pcd/pcd mouse. Dev Neurobiol 67(7):839–859PubMedCrossRefGoogle Scholar
  57. 57.
    Cameron HA, McKay RD (2001) Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. J Comp Neurol 435(4):406–417PubMedCrossRefGoogle Scholar
  58. 58.
    Filippov V, Kronenberg G, Pivneva T, Reuter K, Steiner B, Wang LP, Yamaguchi M, Kettenmann H, Kempermann G (2003) Subpopulation of nestin-expressing progenitor cells in the adult murine hippocampus shows electrophysiological and morphological characteristics of astrocytes. Mol Cell Neurosci 23(3):373–382PubMedCrossRefGoogle Scholar
  59. 59.
    Han YG, Spassky N, Romaguera-Ros M, Garcia-Verdugo JM, Aguilar A, Schneider-Maunoury S, Alvarez-Buylla A (2008) Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells. Nat Neurosci 11(3):277–284PubMedCrossRefGoogle Scholar
  60. 60.
    Amador-Arjona A, Elliott J, Miller A, Ginbey A, Pazour GJ, Enikolopov G, Roberts AJ, Terskikh AV (2011) Primary cilia regulate proliferation of amplifying progenitors in adult hippocampus: implications for learning and memory. J Neurosci 31(27):9933–9944PubMedCrossRefGoogle Scholar
  61. 61.
    Kronenberg G, Reuter K, Steiner B, Brandt MD, Jessberger S, Yamaguchi M, Kempermann G (2003) Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli. J Comp Neurol 467(4):455–463PubMedCrossRefGoogle Scholar
  62. 62.
    Plumpe T, Ehninger D, Steiner B, Klempin F, Jessberger S, Brandt M, Romer B, Rodriguez GR, Kronenberg G, Kempermann G (2006) Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation. BMC Neurosci 7:77PubMedCrossRefGoogle Scholar
  63. 63.
    Hastings NB, Gould E (1999) Rapid extension of axons into the CA3 region by adult-generated granule cells. J Comp Neurol 413(1):146–154PubMedCrossRefGoogle Scholar
  64. 64.
    Forster E, Jossin Y, Zhao S, Chai X, Frotscher M, Goffinet AM (2006) Recent progress in understanding the role of Reelin in radial neuronal migration, with specific emphasis on the dentate gyrus. Eur J Neurosci 23(4):901–909PubMedCrossRefGoogle Scholar
  65. 65.
    Zhao C, Teng EM, Summers RG Jr, Ming GL, Gage FH (2006) Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus I. J Neurosci 26(1):3–11PubMedCrossRefGoogle Scholar
  66. 66.
    Ide Y, Fujiyama F, Okamoto-Furuta K, Tamamaki N, Kaneko T, Hisatsune T (2008) Rapid integration of young newborn dentate gyrus granule cells in the adult hippocampal circuitry. Eur J Neurosci 28(12):2381–2392PubMedCrossRefGoogle Scholar
  67. 67.
    Biebl M, Cooper CM, Winkler J, Kuhn HG (2000) Analysis of neurogenesis and programmed cell death reveals a self-renewing capacity in the adult rat brain. Neurosci Lett 291(1):17–20PubMedCrossRefGoogle Scholar
  68. 68.
    Kee N, Teixeira CM, Wang AH, Frankland PW (2007) Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. Nat Neurosci 10(3):355–362PubMedCrossRefGoogle Scholar
  69. 69.
    Mu Y, Lee SW, Gage FH (2010) Signaling in adult neurogenesis. Curr Opin Neurobiol 20(4):416–423PubMedCrossRefGoogle Scholar
  70. 70.
    Ming GL, Song H (2011) Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 70(4):687–702PubMedCrossRefGoogle Scholar
  71. 71.
    Sun J, Sun J, Ming GL, Song H (2011) Epigenetic regulation of neurogenesis in the adult mammalian brain. Eur J Neurosci 33(6):1087–1093PubMedCrossRefGoogle Scholar
  72. 72.
    Ninkovic J, Gotz M (2007) Signaling in adult neurogenesis: from stem cell niche to neuronal networks. Curr Opin Neurobiol 17(3):338–344PubMedCrossRefGoogle Scholar
  73. 73.
    Llorens-Martin M, Torres-Aleman I, Trejo JL (2009) Mechanisms mediating brain plasticity: IGF1 and adult hippocampal neurogenesis. Neuroscientist 15(2):134–148PubMedCrossRefGoogle Scholar
  74. 74.
    Olson AK, Eadie BD, Ernst C, Christie BR (2006) Environmental enrichment and voluntary exercise massively increase neurogenesis in the adult hippocampus via dissociable pathways. Hippocampus 16(3):250–260PubMedCrossRefGoogle Scholar
  75. 75.
    Park HR, Lee J (2011) Neurogenic contributions made by dietary regulation to hippocampal neurogenesis. Ann N Y Acad Sci 1229:23–28PubMedCrossRefGoogle Scholar
  76. 76.
    Gheusi G, Ortega-Perez I, Murray K, Lledo PM (2009) A niche for adult neurogenesis in social behavior. Behav Brain Res 200(2):315–322PubMedCrossRefGoogle Scholar
  77. 77.
    Schoenfeld TJ, Gould E (2011) Stress, stress hormones, and adult neurogenesis. Exp Neurol 233(1):12–21Google Scholar
  78. 78.
    Martoncikova M, Lievajova K, Orendacova J, Blasko J, Racekova E (2011) Odor enrichment influences neurogenesis in the rostral migratory stream of young rats. Acta Histochem 113(3):326–332PubMedCrossRefGoogle Scholar
  79. 79.
    Bovetti S, Veyrac A, Peretto P, Fasolo A, De MS (2009) Olfactory enrichment influences adult neurogenesis modulating GAD67 and plasticity-related molecules expression in newborn cells of the olfactory bulb. PLoS One 4(7):e6359PubMedCrossRefGoogle Scholar
  80. 80.
    Lee SW, Clemenson GD, Gage FH (2011) New neurons in an aged brain. Behav Brain Res 227(2):497–507Google Scholar
  81. 81.
    Yoneyama M, Shiba T, Hasebe S, Ogita K (2011) Adult neurogenesis is regulated by endogenous factors produced during neurodegeneration. J Pharmacol Sci 115(4):425–432PubMedCrossRefGoogle Scholar
  82. 82.
    Russo I, Barlati S, Bosetti F (2011) Effects of neuroinflammation on the regenerative capacity of brain stem cells. J Neurochem 116(6):947–956Google Scholar
  83. 83.
    Whitney NP, Eidem TM, Peng H, Huang Y, Zheng JC (2009) Inflammation mediates varying effects in neurogenesis: relevance to the pathogenesis of brain injury and neurodegenerative disorders. J Neurochem 108(6):1343–1359PubMedCrossRefGoogle Scholar
  84. 84.
    Sierra A, Encinas JM, Deudero JJ, Chancey JH, Enikolopov G, Overstreet-Wadiche LS, Tsirka SE, Maletic-Savatic M (2010) Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell 7(4):483–495PubMedCrossRefGoogle Scholar
  85. 85.
    Blakemore WF (1969) The ultrastructure of the subependymal plate in the rat. J Anat 104(Pt 3):423–433PubMedGoogle Scholar
  86. 86.
    Peretto P, Merighi A, Fasolo A, Bonfanti L (1999) The subependymal layer in rodents: a site of structural plasticity and cell migration in the adult mammalian brain. Brain Res Bull 49(4):221–243PubMedCrossRefGoogle Scholar
  87. 87.
    Mercier F, Kitasako JT, Hatton GI (2002) Anatomy of the brain neurogenic zones revisited: fractones and the fibroblast/macrophage network. J Comp Neurol 451(2):170–188PubMedCrossRefGoogle Scholar
  88. 88.
    Goings GE, Kozlowski DA, Szele FG (2006) Differential activation of microglia in neurogenic versus non-neurogenic regions of the forebrain. Glia 54(4):329–342PubMedCrossRefGoogle Scholar
  89. 89.
    Marshall GP, Demir M, Steindler DA, Laywell ED (2008) Subventricular zone microglia possess a unique capacity for massive in vitro expansion. Glia 56(16):1799–1808PubMedCrossRefGoogle Scholar
  90. 90.
    Thored P, Heldmann U, Gomes-Leal W, Gisler R, Darsalia V, Taneera J, Nygren JM, Jacobsen SE, Ekdahl CT, Kokaia Z, Lindvall O (2009) Long-term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke. Glia 57(8):835–849PubMedCrossRefGoogle Scholar
  91. 91.
    Bulloch K, Miller MM, Gal-Toth J, Milner TA, Gottfried-Blackmore A, Waters EM, Kaunzner UW, Liu K, Lindquist R, Nussenzweig MC, Steinman RM, McEwen BS (2008) CD11c/EYFP transgene illuminates a discrete network of dendritic cells within the embryonic, neonatal, adult, and injured mouse brain. J Comp Neurol 508(5):687–710PubMedCrossRefGoogle Scholar
  92. 92.
    Rasmussen S, Imitola J, Ayuso-Sacido A, Wang Y, Starossom SC, Kivisakk P, Zhu B, Meyer M, Bronson RT, Garcia-Verdugo JM, Khoury SJ (2011) Reversible neural stem cell niche dysfunction in a model of multiple sclerosis. Ann Neurol 69(5):878–891PubMedCrossRefGoogle Scholar
  93. 93.
    Goncalves MB, Williams EJ, Yip P, Yanez-Munoz RJ, Williams G, Doherty P (2010) The COX-2 inhibitors, meloxicam and nimesulide, suppress neurogenesis in the adult mouse brain. Br J Pharmacol 159(5):1118–1125PubMedCrossRefGoogle Scholar
  94. 94.
    Walton NM, Sutter BM, Laywell ED, Levkoff LH, Kearns SM, Marshall GP, Scheffler B, Steindler DA (2006) Microglia instruct subventricular zone neurogenesis. Glia 54(8):815–825PubMedCrossRefGoogle Scholar
  95. 95.
    Lledo PM, Saghatelyan A, Lemasson M (2004) Inhibitory interneurons in the olfactory bulb: from development to function. Neuroscientist 10(4):292–303PubMedCrossRefGoogle Scholar
  96. 96.
    Wu CH, Chien HF, Chang CY, Ling EA (1997) Heterogeneity of antigen expression and lectin labeling on microglial cells in the olfactory bulb of adult rats. Neurosci Res 28(1):67–75PubMedCrossRefGoogle Scholar
  97. 97.
    Ziv Y, Ron N, Butovsky O, Landa G, Sudai E, Greenberg N, Cohen H, Kipnis J, Schwartz M (2006) Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat Neurosci 9(2):268–275PubMedCrossRefGoogle Scholar
  98. 98.
    Muzio L, Cavasinni F, Marinaro C, Bergamaschi A, Bergami A, Porcheri C, Cerri F, Dina G, Quattrini A, Comi G, Furlan R, Martino G (2010) Cxcl10 enhances blood cells migration in the sub-ventricular zone of mice affected by experimental autoimmune encephalomyelitis. Mol Cell Neurosci 43(3):268–280PubMedCrossRefGoogle Scholar
  99. 99.
    Ziv Y, Schwartz M (2008) Orchestrating brain-cell renewal: the role of immune cells in adult neurogenesis in health and disease. Trends Mol Med 14(11):471–478PubMedCrossRefGoogle Scholar
  100. 100.
    Butovsky O, Ziv Y, Schwartz A, Landa G, Talpalar AE, Pluchino S, Martino G, Schwartz M (2006) Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells. Mol Cell Neurosci 31(1):149–160PubMedCrossRefGoogle Scholar
  101. 101.
    Li L, Walker TL, Zhang Y, Mackay EW, Bartlett PF (2010) Endogenous interferon gamma directly regulates neural precursors in the non-inflammatory brain. J Neurosci 30(27):9038–9050PubMedGoogle Scholar
  102. 102.
    Iosif RE, Ahlenius H, Ekdahl CT, Darsalia V, Thored P, Jovinge S, Kokaia Z, Lindvall O (2008) Suppression of stroke-induced progenitor proliferation in adult subventricular zone by tumor necrosis factor receptor 1. J Cereb Blood Flow Metab 28(9):1574–1587PubMedCrossRefGoogle Scholar
  103. 103.
    Ben-Hur T, Cialic R, Weidenfeld J (2003) Virus and host factors that mediate the clinical and behavioral signs of experimental herpetic encephalitis. A short auto-review. Acta Microbiol Immunol Hung 50(4):443–451PubMedCrossRefGoogle Scholar
  104. 104.
    Bernardino L, Agasse F, Silva B, Ferreira R, Grade S, Malva JO (2008) Tumor necrosis factor-alpha modulates survival, proliferation, and neuronal differentiation in neonatal subventricular zone cell cultures. Stem Cells 26(9):2361–2371PubMedCrossRefGoogle Scholar
  105. 105.
    Wong G, Goldshmit Y, Turnley AM (2004) Interferon-gamma but not TNF alpha promotes neuronal differentiation and neurite outgrowth of murine adult neural stem cells. Exp Neurol 187(1):171–177PubMedCrossRefGoogle Scholar
  106. 106.
    Widera D, Mikenberg I, Elvers M, Kaltschmidt C, Kaltschmidt B (2006) Tumor necrosis factor alpha triggers proliferation of adult neural stem cells via IKK/NF-kappaB signaling. BMC Neurosci 7:64PubMedCrossRefGoogle Scholar
  107. 107.
    Wu JP, Kuo JS, Liu YL, Tzeng SF (2000) Tumor necrosis factor-alpha modulates the proliferation of neural progenitors in the subventricular/ventricular zone of adult rat brain. Neurosci Lett 292(3):203–206PubMedCrossRefGoogle Scholar
  108. 108.
    Iosif RE, Ekdahl CT, Ahlenius H, Pronk CJ, Bonde S, Kokaia Z, Jacobsen SE, Lindvall O (2006) Tumor necrosis factor receptor 1 is a negative regulator of progenitor proliferation in adult hippocampal neurogenesis. J Neurosci 26(38):9703–9712PubMedCrossRefGoogle Scholar
  109. 109.
    Bowen KK, Dempsey RJ, Vemuganti R (2011) Adult interleukin-6 knockout mice show compromised neurogenesis. NeuroReport 22(3):126–130PubMedCrossRefGoogle Scholar
  110. 110.
    Widera D, Holtkamp W, Entschladen F, Niggemann B, Zanker K, Kaltschmidt B, Kaltschmidt C (2004) MCP-1 induces migration of adult neural stem cells. Eur J Cell Biol 83(8):381–387PubMedCrossRefGoogle Scholar
  111. 111.
    Liu XS, Zhang ZG, Zhang RL, Gregg SR, Wang L, Yier T, Chopp M (2007) Chemokine ligand 2 (CCL2) induces migration and differentiation of subventricular zone cells after stroke. J Neurosci Res 85(10):2120–2125PubMedCrossRefGoogle Scholar
  112. 112.
    Olah M, Ping G, de Haas AH, Brouwer N, Meerlo P, Van Der Zee EA, Biber K, Boddeke HW (2009) Enhanced hippocampal neurogenesis in the absence of microglia T cell interaction and microglia activation in the murine running wheel model. Glia 57(10):1046–1061PubMedCrossRefGoogle Scholar
  113. 113.
    Sasaki T, Kitagawa K, Sugiura S, Omura-Matsuoka E, Tanaka S, Yagita Y, Okano H, Matsumoto M, Hori M (2003) Implication of cyclooxygenase-2 on enhanced proliferation of neural progenitor cells in the adult mouse hippocampus after ischemia. J Neurosci Res 72(4):461–471PubMedCrossRefGoogle Scholar
  114. 114.
    McPherson CA, Kraft AD, Harry GJ (2011) Injury-induced neurogenesis: consideration of resident microglia as supportive of neural progenitor cells. Neurotox Res 19(2):341–352PubMedCrossRefGoogle Scholar
  115. 115.
    Bachstetter AD, Morganti JM, Jernberg J, Schlunk A, Mitchell SH, Brewster KW, Hudson CE, Cole MJ, Harrison JK, Bickford PC, Gemma C (2009) Fractalkine and CX(3)CR1 regulate hippocampal neurogenesis in adult and aged rats. Neurobiol Aging 32(11):2030–2044Google Scholar
  116. 116.
    Wolf SA, Steiner B, Akpinarli A, Kammertoens T, Nassenstein C, Braun A, Blankenstein T, Kempermann G (2009) CD4-positive T lymphocytes provide a neuroimmunological link in the control of adult hippocampal neurogenesis. J Immunol 182(7):3979–3984PubMedCrossRefGoogle Scholar
  117. 117.
    Kiyota T, Ingraham KL, Swan RJ, Jacobsen MT, Andrews SJ, Ikezu T (2011) AAV serotype 2/1-mediated gene delivery of anti-inflammatory interleukin-10 enhances neurogenesis and cognitive function in APP + PS1 mice. Gene Ther. doi:  10.1038/gt.2011.126 (In Press)
  118. 118.
    Beck RD Jr, Wasserfall C, Ha GK, Cushman JD, Huang Z, Atkinson MA, Petitto JM (2005) Changes in hippocampal IL-15, related cytokines, and neurogenesis in IL-2 deficient mice. Brain Res 1041(2):223–230PubMedCrossRefGoogle Scholar
  119. 119.
    Basu A, Krady JK, Levison SW (2004) Interleukin-1: a master regulator of neuroinflammation. J Neurosci Res 78(2):151–156PubMedCrossRefGoogle Scholar
  120. 120.
    Gemma C, Bachstetter AD, Cole MJ, Fister M, Hudson C, Bickford PC (2007) Blockade of caspase-1 increases neurogenesis in the aged hippocampus. Eur J Neurosci 26(10):2795–2803PubMedCrossRefGoogle Scholar
  121. 121.
    Kuzumaki N, Ikegami D, Imai S, Narita M, Tamura R, Yajima M, Suzuki A, Miyashita K, Niikura K, Takeshima H, Ando T, Ushijima T, Suzuki T, Narita M (2010) Enhanced IL-1beta production in response to the activation of hippocampal glial cells impairs neurogenesis in aged mice. Synapse 64(9):721–728PubMedGoogle Scholar
  122. 122.
    Koo JW, Duman RS (2008) IL-1beta is an essential mediator of the antineurogenic and anhedonic effects of stress. Proc Natl Acad Sci U S A 105(2):751–756PubMedCrossRefGoogle Scholar
  123. 123.
    Mathieu P, Battista D, Depino A, Roca V, Graciarena M, Pitossi F (2010) The more you have, the less you get: the functional role of inflammation on neuronal differentiation of endogenous and transplanted neural stem cells in the adult brain. J Neurochem 112(6):1368–1385PubMedCrossRefGoogle Scholar
  124. 124.
    Maggi L, Scianni M, Branchi I, D’Andrea I, Lauro C, Limatola C (2011) CX(3)CR1 deficiency alters hippocampal-dependent plasticity phenomena blunting the effects of enriched environment. Front Cell Neurosci 5:22PubMedCrossRefGoogle Scholar
  125. 125.
    Pitossi F, del RA, Kabiersch A, Besedovsky H (1997) Induction of cytokine transcripts in the central nervous system and pituitary following peripheral administration of endotoxin to mice. J Neurosci Res 48(4):287–298PubMedCrossRefGoogle Scholar
  126. 126.
    Arguello AA, Fischer SJ, Schonborn JR, Markus RW, Brekken RA, Eisch AJ (2009) Effect of chronic morphine on the dentate gyrus neurogenic microenvironment. Neuroscience 159(3):1003–1010PubMedCrossRefGoogle Scholar
  127. 127.
    Spulber S, Oprica M, Bartfai T, Winblad B, Schultzberg M (2008) Blunted neurogenesis and gliosis due to transgenic overexpression of human soluble IL-1ra in the mouse. Eur J Neurosci 27(3):549–558PubMedCrossRefGoogle Scholar
  128. 128.
    Vallieres L, Rivest S (1997) Regulation of the genes encoding interleukin-6, its receptor, and gp130 in the rat brain in response to the immune activator lipopolysaccharide and the proinflammatory cytokine interleukin-1beta. J Neurochem 69(4):1668–1683PubMedCrossRefGoogle Scholar
  129. 129.
    Vallieres L, Campbell IL, Gage FH, Sawchenko PE (2002) Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6. J Neurosci 22(2):486–492PubMedGoogle Scholar
  130. 130.
    Seguin JA, Brennan J, Mangano E, Hayley S (2009) Proinflammatory cytokines differentially influence adult hippocampal cell proliferation depending upon the route and chronicity of administration. Neuropsychiatr Dis Treat 5:5–14PubMedGoogle Scholar
  131. 131.
    Baron R, Nemirovsky A, Harpaz I, Cohen H, Owens T, Monsonego A (2008) IFN-gamma enhances neurogenesis in wild-type mice and in a mouse model of Alzheimer’s disease. FASEB J 22(8):2843–2852PubMedCrossRefGoogle Scholar
  132. 132.
    Harry GJ (2008) Lefebvre, d.C., McPherson, C.A., Funk, J.A., Aoyama, M., Wine, R.N.: Tumor necrosis factor p55 and p75 receptors are involved in chemical-induced apoptosis of dentate granule neurons. J Neurochem 106(1):281–298PubMedCrossRefGoogle Scholar
  133. 133.
    Cacci E, Claasen JH, Kokaia Z (2005) Microglia-derived tumor necrosis factor-alpha exaggerates death of newborn hippocampal progenitor cells in vitro. J Neurosci Res 80(6):789–797PubMedCrossRefGoogle Scholar
  134. 134.
    Bravo JA, Parra CS, Arancibia S, Andres S, Morales P, Herrera-Marschitz M, Herrera L, Lara HE, Fiedler JL (2006) Adrenalectomy promotes a permanent decrease of plasma corticoid levels and a transient increase of apoptosis and the expression of Transforming Growth Factor beta1 (TGF-beta1) in hippocampus: effect of a TGF-beta1 oligo-antisense. BMC Neurosci 7:40PubMedCrossRefGoogle Scholar
  135. 135.
    Bye N, Zieba M, Wreford NG, Nichols NR (2001) Resistance of the dentate gyrus to induced apoptosis during ageing is associated with increases in transforming growth factor-beta1 messenger RNA. Neuroscience 105(4):853–862PubMedCrossRefGoogle Scholar
  136. 136.
    Buckwalter MS, Yamane M, Coleman BS, Ormerod BK, Chin JT, Palmer T, Wyss-Coray T (2006) Chronically increased transforming growth factor-beta1 strongly inhibits hippocampal neurogenesis in aged mice. Am J Pathol 169(1):154–164PubMedCrossRefGoogle Scholar
  137. 137.
    Wachs FP, Winner B, Couillard-Despres S, Schiller T, Aigner R, Winkler J, Bogdahn U, Aigner L (2006) Transforming growth factor-beta1 is a negative modulator of adult neurogenesis. J Neuropathol Exp Neurol 65(4):358–370PubMedCrossRefGoogle Scholar
  138. 138.
    Graciarena M, Depino AM, Pitossi FJ (2010) Prenatal inflammation impairs adult neurogenesis and memory related behavior through persistent hippocampal TGFbeta1 downregulation. Brain Behav Immun 24(8):1301–1309PubMedCrossRefGoogle Scholar
  139. 139.
    Battista D, Ferrari CC, Gage FH, Pitossi FJ (2006) Neurogenic niche modulation by activated microglia: transforming growth factor beta increases neurogenesis in the adult dentate gyrus. Eur J Neurosci 23(1):83–93PubMedCrossRefGoogle Scholar
  140. 140.
    Valero J, España J, Parra-Damas A, Martín E, Rodríguez-Álvarez J, Saura CA (2011) Short-term Environmental Enrichment Rescues Adult Neurogenesis and Memory Deficits in APPSw,Ind Transgenic Mice. PLoS One 6(2):e16832Google Scholar
  141. 141.
    Kempermann G, Kuhn HG, Gage FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386(6624):493–495PubMedCrossRefGoogle Scholar
  142. 142.
    Kronenberg G, Bick-Sander A, Bunk E, Wolf C, Ehninger D, Kempermann G (2006) Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus. Neurobiol Aging 27(10):1505–1513PubMedCrossRefGoogle Scholar
  143. 143.
    Llorens-Martin M, Torres-Aleman I, Trejo JL (2010) Exercise modulates insulin-like growth factor 1-dependent and -independent effects on adult hippocampal neurogenesis and behaviour. Mol Cell Neurosci 44(2):109–117PubMedCrossRefGoogle Scholar
  144. 144.
    Brown J, Cooper-Kuhn CM, Kempermann G, van PH, Winkler J, Gage FH, Kuhn HG (2003) Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis. Eur J Neurosci 17(10):2042–2046PubMedCrossRefGoogle Scholar
  145. 145.
    Lazarov O, Robinson J, Tang YP, Hairston IS, Korade-Mirnics Z, Lee VM, Hersh LB, Sapolsky RM, Mirnics K, Sisodia SS (2005) Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice. Cell 120(5):701–713PubMedCrossRefGoogle Scholar
  146. 146.
    Lahiani-Cohen I, Lourbopoulos A, Haber E, Rozenstein-Tsalkovich L, Abramsky O, Grigoriadis N, Rosenmann H (2011) Moderate environmental enrichment mitigates tauopathy in a neurofibrillary tangle mouse model. J Neuropathol Exp Neurol 70(7):610–621PubMedCrossRefGoogle Scholar
  147. 147.
    Lyons A, Lynch AM, Downer EJ, Hanley R, O’Sullivan JB, Smith A, Lynch MA (2009) Fractalkine-induced activation of the phosphatidylinositol-3 kinase pathway attentuates microglial activation in vivo and in vitro. J Neurochem 110(5):1547–1556PubMedCrossRefGoogle Scholar
  148. 148.
    Bachstetter AD, Pabon MM, Cole MJ, Hudson CE, Sanberg PR, Willing AE, Bickford PC, Gemma C (2008) Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain. BMC Neurosci 9:22PubMedCrossRefGoogle Scholar
  149. 149.
    Trejo JL, Llorens-Martin MV, Torres-Aleman I (2008) The effects of exercise on spatial learning and anxiety-like behavior are mediated by an IGF-I-dependent mechanism related to hippocampal neurogenesis. Mol Cell Neurosci 37(2):402–411PubMedCrossRefGoogle Scholar
  150. 150.
    Kohman RA, Deyoung EK, Bhattacharya TK, Peterson LN, Rhodes JS (2011) Wheel running attenuates microglia proliferation and increases expression of a proneurogenic phenotype in the hippocampus of aged mice. Brain Behav Immun (In Press)Google Scholar
  151. 151.
    Choi YS, Cho HY, Hoyt KR, Naegele JR, Obrietan K (2008) IGF-1 receptor-mediated ERK/MAPK signaling couples status epilepticus to progenitor cell proliferation in the subgranular layer of the dentate gyrus. Glia 56(7):791–800PubMedCrossRefGoogle Scholar
  152. 152.
    Singh AK, Jiang Y (2004) How does peripheral lipopolysaccharide induce gene expression in the brain of rats? Toxicology 201(1–3):197–207PubMedCrossRefGoogle Scholar
  153. 153.
    Mori K, Kaneko YS, Nakashima A, Nagatsu T, Nagatsu I, Ota A (2010) Peripherally injected lipopolysaccharide induces apoptosis in the subventricular zone of young adult mice. Neurosci Lett 481(2):126–130PubMedCrossRefGoogle Scholar
  154. 154.
    Monje ML, Toda H, Palmer TD (2003) Inflammatory blockade restores adult hippocampal neurogenesis. Science 302(5651):1760–1765PubMedCrossRefGoogle Scholar
  155. 155.
    Cacci E, Ajmone-Cat MA, Anelli T, Biagioni S, Minghetti L (2008) In vitro neuronal and glial differentiation from embryonic or adult neural precursor cells are differently affected by chronic or acute activation of microglia. Glia 56(4):412–425PubMedCrossRefGoogle Scholar
  156. 156.
    Keene CD, Chang R, Stephen C, Nivison M, Nutt SE, Look A, Breyer RM, Horner PJ, Hevner R, Montine TJ (2009) Protection of hippocampal neurogenesis from toll-like receptor 4-dependent innate immune activation by ablation of prostaglandin E2 receptor subtype EP1 or EP2. Am J Pathol 174(6):2300–2309PubMedCrossRefGoogle Scholar
  157. 157.
    Packer MA, Stasiv Y, Benraiss A, Chmielnicki E, Grinberg A, Westphal H, Goldman SA, Enikolopov G (2003) Nitric oxide negatively regulates mammalian adult neurogenesis. Proc Natl Acad Sci U S A 100(16):9566–9571PubMedCrossRefGoogle Scholar
  158. 158.
    Carreira BP, Morte MI, Inacio A, Costa G, Rosmaninho-Salgado J, Agasse F, Carmo A, Couceiro P, Brundin P, Ambrosio AF, Carvalho CM, Araujo IM (2010) Nitric oxide stimulates the proliferation of neural stem cells bypassing the epidermal growth factor receptor. Stem Cells 28(7):1219–1230PubMedGoogle Scholar
  159. 159.
    Sun Y, Jin K, Childs JT, Xie L, Mao XO, Greenberg DA (2005) Neuronal nitric oxide synthase and ischemia-induced neurogenesis. J Cereb Blood Flow Metab 25(4):485–492PubMedCrossRefGoogle Scholar
  160. 160.
    Hoffmann O, Mahrhofer C, Rueter N, Freyer D, Bert B, Fink H, Weber JR (2007) Pneumococcal cell wall-induced meningitis impairs adult hippocampal neurogenesis. Infect Immun 75(9):4289–4297PubMedCrossRefGoogle Scholar
  161. 161.
    Ekdahl CT, Kokaia Z, Lindvall O (2009) Brain inflammation and adult neurogenesis: the dual role of microglia. Neuroscience 158(3):1021–1029PubMedCrossRefGoogle Scholar
  162. 162.
    Qiu L, Zhu C, Wang X, Xu F, Eriksson PS, Nilsson M, Cooper-Kuhn CM, Kuhn HG, Blomgren K (2007) Less neurogenesis and inflammation in the immature than in the juvenile brain after cerebral hypoxia-ischemia. J Cereb Blood Flow Metab 27(4):785–794PubMedGoogle Scholar
  163. 163.
    Liu Z, Fan Y, Won SJ, Neumann M, Hu D, Zhou L, Weinstein PR, Liu J (2007) Chronic treatment with minocycline preserves adult new neurons and reduces functional impairment after focal cerebral ischemia. Stroke 38(1):146–152PubMedCrossRefGoogle Scholar
  164. 164.
    Hoehn BD, Palmer TD, Steinberg GK (2005) Neurogenesis in rats after focal cerebral ischemia is enhanced by indomethacin. Stroke 36(12):2718–2724PubMedCrossRefGoogle Scholar
  165. 165.
    Kim BJ, Kim MJ, Park JM, Lee SH, Kim YJ, Ryu S, Kim YH, Yoon BW (2009) Reduced neurogenesis after suppressed inflammation by minocycline in transient cerebral ischemia in rat. J Neurol Sci 279(1–2):70–75PubMedCrossRefGoogle Scholar
  166. 166.
    Deierborg T, Roybon L, Inacio AR, Pesic J, Brundin P (2010) Brain injury activates microglia that induce neural stem cell proliferation ex vivo and promote differentiation of neurosphere-derived cells into neurons and oligodendrocytes. Neuroscience 171(4):1386–1396PubMedCrossRefGoogle Scholar
  167. 167.
    Yan YP, Sailor KA, Vemuganti R, Dempsey RJ (2006) Insulin-like growth factor-1 is an endogenous mediator of focal ischemia-induced neural progenitor proliferation. Eur J Neurosci 24(1):45–54PubMedCrossRefGoogle Scholar
  168. 168.
    Yan YP, Lang BT, Vemuganti R, Dempsey RJ (2009) Galectin-3 mediates post-ischemic tissue remodeling. Brain Res 1288:116–124PubMedCrossRefGoogle Scholar
  169. 169.
    Yan YP, Sailor KA, Lang BT, Park SW, Vemuganti R, Dempsey RJ (2007) Monocyte chemoattractant protein-1 plays a critical role in neuroblast migration after focal cerebral ischemia. J Cereb Blood Flow Metab 27(6):1213–1224PubMedCrossRefGoogle Scholar
  170. 170.
    Yan YP, Lang BT, Vemuganti R, Dempsey RJ (2009) Osteopontin is a mediator of the lateral migration of neuroblasts from the subventricular zone after focal cerebral ischemia. Neurochem Int 55(8):826–832PubMedCrossRefGoogle Scholar
  171. 171.
    Parent JM, Yu TW, Leibowitz RT, Geschwind DH, Sloviter RS, Lowenstein DH (1997) Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci 17(10):3727–3738PubMedGoogle Scholar
  172. 172.
    Bonde S, Ekdahl CT, Lindvall O (2006) Long-term neuronal replacement in adult rat hippocampus after status epilepticus despite chronic inflammation. Eur J Neurosci 23(4):965–974PubMedCrossRefGoogle Scholar
  173. 173.
    Ekdahl CT, Claasen JH, Bonde S, Kokaia Z, Lindvall O (2003) Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci U S A 100(23):13632–13637PubMedCrossRefGoogle Scholar
  174. 174.
    Yang F, Liu ZR, Chen J, Zhang SJ, Quan QY, Huang YG, Jiang W (2010) Roles of astrocytes and microglia in seizure-induced aberrant neurogenesis in the hippocampus of adult rats. J Neurosci Res 88(3):519–529PubMedGoogle Scholar
  175. 175.
    Jung KH, Chu K, Lee ST, Kim J, Sinn DI, Kim JM, Park DK, Lee JJ, Kim SU, Kim M, Lee SK, Roh JK (2006) Cyclooxygenase-2 inhibitor, celecoxib, inhibits the altered hippocampal neurogenesis with attenuation of spontaneous recurrent seizures following pilocarpine-induced status epilepticus. Neurobiol Dis 23(2):237–246PubMedCrossRefGoogle Scholar
  176. 176.
    Zhang HJ, Sun RP, Lei GF, Yang L, Liu CX (2008) Cyclooxygenase-2 inhibitor inhibits hippocampal synaptic reorganization in pilocarpine-induced status epilepticus rats. J Zhejiang Univ Sci B 9(11):903–915PubMedCrossRefGoogle Scholar
  177. 177.
    Rola R, Raber J, Rizk A, Otsuka S, VandenBerg SR, Morhardt DR, Fike JR (2004) Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice. Exp Neurol 188(2):316–330PubMedCrossRefGoogle Scholar
  178. 178.
    Mizumatsu S, Monje ML, Morhardt DR, Rola R, Palmer TD, Fike JR (2003) Extreme sensitivity of adult neurogenesis to low doses of X-irradiation. Cancer Res 63(14):4021–4027PubMedGoogle Scholar
  179. 179.
    Ramanan S, Kooshki M, Zhao W, Hsu FC, Riddle DR, Robbins ME (2009) The PPARalpha agonist fenofibrate preserves hippocampal neurogenesis and inhibits microglial activation after whole-brain irradiation. Int J Radiat Oncol Biol Phys 75(3):870–877PubMedCrossRefGoogle Scholar
  180. 180.
    Hellstrom NA, Lindberg OR, Stahlberg A, Swanpalmer J, Pekny M, Blomgren K, Kuhn HG (2011) Unique gene expression patterns indicate microglial contribution to neural stem cell recovery following irradiation. Mol Cell Neurosci 46(4):710–719PubMedCrossRefGoogle Scholar
  181. 181.
    Enwere E, Shingo T, Gregg C, Fujikawa H, Ohta S, Weiss S (2004) Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. J Neurosci 24(38):8354–8365PubMedCrossRefGoogle Scholar
  182. 182.
    Drapeau E, Mayo W, Aurousseau C, Le MM, Piazza PV, Abrous DN (2003) Spatial memory performances of aged rats in the water maze predict levels of hippocampal neurogenesis. Proc Natl Acad Sci U S A 100(24):14385–14390PubMedCrossRefGoogle Scholar
  183. 183.
    Hattiangady B, Shetty AK (2008) Aging does not alter the number or phenotype of putative stem/progenitor cells in the neurogenic region of the hippocampus. Neurobiol Aging 29(1):129–147PubMedCrossRefGoogle Scholar
  184. 184.
    Jin K, Sun Y, Xie L, Batteur S, Mao XO, Smelick C, Logvinova A, Greenberg DA (2003) Neurogenesis and aging: FGF-2 and HB-EGF restore neurogenesis in hippocampus and subventricular zone of aged mice. Aging Cell 2(3):175–183PubMedCrossRefGoogle Scholar
  185. 185.
    Lichtenwalner RJ, Forbes ME, Bennett SA, Lynch CD, Sonntag WE, Riddle DR (2001) Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis. Neuroscience 107(4):603–613PubMedCrossRefGoogle Scholar
  186. 186.
    Kempermann G, Kuhn HG, Gage FH (1998) Experience-induced neurogenesis in the senescent dentate gyrus. J Neurosci 18(9):3206–3212PubMedGoogle Scholar
  187. 187.
    Encinas JM, Michurina TV, Peunova N, Park JH, Tordo J, Peterson DA, Fishell G, Koulakov A, Enikolopov G (2011) Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus. Cell Stem Cell 8(5):566–579PubMedCrossRefGoogle Scholar
  188. 188.
    Gemma C, Bachstetter AD, Bickford PC (2010) Neuron-Microglia Dialogue and Hippocampal Neurogenesis in the Aged Brain. Aging Dis 1(3):232–244PubMedGoogle Scholar
  189. 189.
    Luo XG, Ding JQ, Chen SD (2010) Microglia in the aging brain: relevance to neurodegeneration. Mol Neurodegener 5:12PubMedCrossRefGoogle Scholar
  190. 190.
    Klempin F, Kempermann G (2007) Adult hippocampal neurogenesis and aging. Eur Arch Psychiatry Clin Neurosci 257(5):271–280PubMedCrossRefGoogle Scholar
  191. 191.
    Sierra A, Gottfried-Blackmore AC, McEwen BS, Bulloch K (2007) Microglia derived from aging mice exhibit an altered inflammatory profile. Glia 55(4):412–424PubMedCrossRefGoogle Scholar
  192. 192.
    Petry KG, Brochet B, Dousset V, Vignes JR, Boiziau C (2010) Inflammation induced neurological handicap processes in multiple sclerosis: new insights from preclinical studies. J Neural Transm 117(8):907–917PubMedCrossRefGoogle Scholar
  193. 193.
    Curtis MA, Penney EB, Pearson AG, van Roon-Mom WM, Butterworth NJ, Dragunow M, Connor B, Faull RL (2003) Increased cell proliferation and neurogenesis in the adult human Huntington’s disease brain. Proc Natl Acad Sci U S A 100(15):9023–9027PubMedCrossRefGoogle Scholar
  194. 194.
    Gil-Mohapel J, Simpson JM, Ghilan M, Christie BR (2011) Neurogenesis in Huntington’s disease: can studying adult neurogenesis lead to the development of new therapeutic strategies? Brain Res 1406:84–105PubMedCrossRefGoogle Scholar
  195. 195.
    Hsiao HY, Chern Y (2010) Targeting glial cells to elucidate the pathogenesis of Huntington’s disease. Mol Neurobiol 41(2–3):248–255PubMedCrossRefGoogle Scholar
  196. 196.
    Depino AM, Earl C, Kaczmarczyk E, Ferrari C, Besedovsky H, del RA, Pitossi FJ, Oertel WH (2003) Microglial activation with atypical proinflammatory cytokine expression in a rat model of Parkinson’s disease. Eur J Neurosci 18(10):2731–2742PubMedCrossRefGoogle Scholar
  197. 197.
    Pott Godoy MC, Tarelli R, Ferrari CC, Sarchi MI, Pitossi FJ (2008) Central and systemic IL-1 exacerbates neurodegeneration and motor symptoms in a model of Parkinson’s disease. Brain 131(Pt 7):1880–1894Google Scholar
  198. 198.
    Selkoe DJ (2002) Alzheimer’s disease is a synaptic failure. Science 298(5594):789–791PubMedCrossRefGoogle Scholar
  199. 199.
    McGeer EG, McGeer PL (2010) Neuroinflammation in Alzheimer's disease and mild cognitive impairment: a field in its infancy. J Alzheimers Dis 19:355–361PubMedGoogle Scholar
  200. 200.
    Rodriguez JJ, Verkhratsky A (2011) Neurogenesis in Alzheimer’s disease. J Anat 219(1):78–89PubMedCrossRefGoogle Scholar
  201. 201.
    Choi SH, Veeraraghavalu K, Lazarov O, Marler S, Ransohoff RM, Ramirez JM, Sisodia SS (2008) Non-cell-autonomous effects of presenilin 1 variants on enrichment-mediated hippocampal progenitor cell proliferation and differentiation. Neuron 59(4):568–580PubMedCrossRefGoogle Scholar
  202. 202.
    Butovsky O, Koronyo-Hamaoui M, Kunis G, Ophir E, Landa G, Cohen H, Schwartz M (2006) Glatiramer acetate fights against Alzheimer’s disease by inducing dendritic-like microglia expressing insulin-like growth factor 1. Proc Natl Acad Sci U S A 103(31):11784–11789PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science + Bussines Media, LLC 2012

Authors and Affiliations

  • Jorge Valero
    • 2
  • Maria Francisca Eiriz
    • 3
  • Tiago Santos
    • 2
  • Ismael Neiva
    • 2
  • Raquel Ferreira
    • 2
  • João O. Malva
    • 1
    Email author
  1. 1.Laboratory of Biochemistry and Cell Biology, Faculty of MedicineCenter for Neuroscience and Cell Biology, University of CoimbraCoimbraPortugal
  2. 2.Center for Neuroscience and Cell Biology, University of CoimbraCoimbraPortugal
  3. 3.MIT-Portugal PhD Program, BioengineeringCenter for Neuroscience and Cell Biology, University of CoimbraCoimbraPortugal

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