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Current perspectives on the link between neuroinflammation and neurogenesis

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Abstract

The link between neuroinflammation and neurogenesis is an area of intensive research in contemporary neuroscience. The burgeoning amount of evidence accumulated over the past decade has been incredible, and now there remains the figuring out of minutia to give us a more complete picture of what individual, synergistic, and antagonistic events are occurring between neurogenesis and neuroinflammation. An intricate study of the inflammatory microenvironment influenced by the presence of the various inflammatory components like cytokines, chemokines, and immune cells is essential for: 1) understanding how neurogenesis can be affected in such a specialized niche and 2) applying the knowledge gained for the treatment of cognitive and/or motor deficits arising from inflammation-associated diseases like stroke, traumatic brain injury, Alzheimer’s disease, and Parkinson’s disease. This review is written to provide the reader with up-to-date information explaining how these inflammatory components are effecting changes on neurogenesis.

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References

  • Aimone JB, Deng W, Gage FH (2011) Resolving new memories: a critical look at the dentate gyrus, adult neurogenesis, and pattern separation. Neuron 70(4):589–596. doi:10.1016/j.neuron.2011.05.010

    PubMed Central  CAS  PubMed  Google Scholar 

  • 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):433–457. doi:10.1002/cne.901370404

    CAS  PubMed  Google Scholar 

  • Altman J, Das GD (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124(3):319–335

    CAS  PubMed  Google Scholar 

  • Ardelt AA, Bhattacharyya BJ, Belmadani A, Ren D, Miller RJ (2013) Stromal derived growth factor-1 (CXCL12) modulates synaptic transmission to immature neurons during post-ischemic cerebral repair. Exp Neurol 248:246–253. doi:10.1016/j.expneurol.2013.06.017

    PubMed Central  CAS  PubMed  Google Scholar 

  • 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):1003–1010. doi:10.1016/j.neuroscience.2009.01.020

    PubMed Central  CAS  PubMed  Google Scholar 

  • Arvidsson A, Kokaia Z, Lindvall O (2001) N-methyl-D-aspartate receptor-mediated increase of neurogenesis in adult rat dentate gyrus following stroke. Eur J NeuroSci 14(1):10–18

    CAS  PubMed  Google Scholar 

  • Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O (2002) Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 8(9):963–970. doi:10.1038/nm747

    CAS  PubMed  Google Scholar 

  • Belmadani A, Tran PB, Ren D, Miller RJ (2006) Chemokines regulate the migration of neural progenitors to sites of neuroinflammation. J Neurosci Off J Soc Neurosci 26(12):3182–3191. doi:10.1523/JNEUROSCI.0156-06.2006

    CAS  Google Scholar 

  • Ben Menachem-Zidon O, Goshen I, Kreisel T, Ben Menahem Y, Reinhartz E, Ben Hur T, Yirmiya R (2008) Intrahippocampal transplantation of transgenic neural precursor cells overexpressing interleukin-1 receptor antagonist blocks chronic isolation-induced impairment in memory and neurogenesis. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 33(9):2251–2262. doi:10.1038/sj.npp.1301606

    CAS  Google Scholar 

  • Ben-Hur T, Ben-Menachem O, Furer V, Einstein O, Mizrachi-Kol R, Grigoriadis N (2003) Effects of proinflammatory cytokines on the growth, fate, and motility of multipotential neural precursor cells. Mol Cell Neurosci 24(3):623–631. doi:10.1016/s1044-7431(03)00218-5

    CAS  PubMed  Google Scholar 

  • Bernier PJ, Bedard A, Vinet J, Levesque M, Parent A (2002) Newly generated neurons in the amygdala and adjoining cortex of adult primates. Proc Natl Acad Sci U S A 99(17):11464–11469. doi:10.1073/pnas.172403999

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bjorklund A, Lindvall O (2000) Cell replacement therapies for central nervous system disorders. Nat Neurosci 3(6):537–544. doi:10.1038/75705

    CAS  PubMed  Google Scholar 

  • Bowen KK, Naylor M, Vemuganti R (2006) Prevention of inflammation is a mechanism of preconditioning-induced neuroprotection against focal cerebral ischemia. Neurochem Int 49(2):127–135. doi:10.1016/j.neuint.2006.02.011

    CAS  PubMed  Google Scholar 

  • Burns JM, Summers BC, Wang Y, Melikian A, Berahovich R, Miao Z, Penfold ME, Sunshine MJ, Littman DR, Kuo CJ, Wei K, McMaster BE, Wright K, Howard MC, Schall TJ (2006) A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med 203(9):2201–2213. doi:10.1084/jem.20052144

    PubMed Central  CAS  PubMed  Google Scholar 

  • 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):149–160. doi:10.1016/j.mcn.2005.10.006

    CAS  PubMed  Google Scholar 

  • 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):789–797. doi:10.1002/jnr.20531

    CAS  PubMed  Google Scholar 

  • 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):412–425. doi:10.1002/glia.20616

    PubMed  Google Scholar 

  • Cepok S, Rosche B, Grummel V, Vogel F, Zhou D, Sayn J, Sommer N, Hartung HP, Hemmer B (2005) Short-lived plasma blasts are the main B cell effector subset during the course of multiple sclerosis. Brain J Neurol 128(Pt 7):1667–1676. doi:10.1093/brain/awh486

    Google Scholar 

  • Chan PH (1996) Role of oxidants in ischemic brain damage. Stroke J Cereb Circ 27(6):1124–1129. doi:10.1161/01.str.27.6.1124

    CAS  Google Scholar 

  • Chen Z, Palmer TD (2013) Differential roles of TNFR1 and TNFR2 signaling in adult hippocampal neurogenesis. Brain Behav Immun 30:45–53. doi:10.1016/j.bbi.2013.01.083

    PubMed Central  CAS  PubMed  Google Scholar 

  • Chen J, Magavi SS, Macklis JD (2004) Neurogenesis of corticospinal motor neurons extending spinal projections in adult mice. Proc Natl Acad Sci U S A 101(46):16357–16362. doi:10.1073/pnas.0406795101

    PubMed Central  CAS  PubMed  Google Scholar 

  • Conover JC, Shook BA (2011) Aging of the subventricular zone neural stem cell niche. Aging Dis 2(1):49–63

    PubMed Central  PubMed  Google Scholar 

  • Conti B, Park LC, Calingasan NY, Kim Y, Kim H, Bae Y, Gibson GE, Joh TH (1999) Cultures of astrocytes and microglia express interleukin 18. Brain Res Mol Brain Res 67(1):46–52

    CAS  PubMed  Google Scholar 

  • Covey MV, Loporchio D, Buono KD, Levison SW (2011) Opposite effect of inflammation on subventricular zone versus hippocampal precursors in brain injury. Ann Neurol 70(4):616–626. doi:10.1002/ana.22473

    PubMed Central  CAS  PubMed  Google Scholar 

  • Deng W, Aimone JB, Gage FH (2010) New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci 11(5):339–350. doi:10.1038/nrn2822

    PubMed Central  CAS  PubMed  Google Scholar 

  • Duan X, Kang E, Liu CY, Ming GL, Song H (2008) Development of neural stem cell in the adult brain. Curr Opin Neurobiol 18(1):108–115. doi:10.1016/j.conb.2008.04.001

    PubMed Central  CAS  PubMed  Google Scholar 

  • Dziembowska M, Tham TN, Lau P, Vitry S, Lazarini F, Dubois-Dalcq M (2005) A role for CXCR4 signaling in survival and migration of neural and oligodendrocyte precursors. Glia 50(3):258–269. doi:10.1002/glia.20170

    CAS  PubMed  Google Scholar 

  • Ekdahl CT, Mohapel P, Elmer E, Lindvall O (2001) Caspase inhibitors increase short-term survival of progenitor-cell progeny in the adult rat dentate gyrus following status epilepticus. Eur J NeuroSci 14(6):937–945

    CAS  PubMed  Google Scholar 

  • 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):13632–13637. doi:10.1073/pnas.2234031100

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ekdahl CT, Kokaia Z, Lindvall O (2009) Brain inflammation and adult neurogenesis: the dual role of microglia. Neuroscience 158(3):1021–1029. doi:10.1016/j.neuroscience.2008.06.052

    CAS  PubMed  Google Scholar 

  • Emsley JG, Mitchell BD, Kempermann G, Macklis JD (2005) Adult neurogenesis and repair of the adult CNS with neural progenitors, precursors, and stem cells. Prog Neurobiol 75(5):321–341. doi:10.1016/j.pneurobio.2005.04.002

    CAS  PubMed  Google Scholar 

  • Engelhardt B, Ransohoff RM (2005) The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends Immunol 26(9):485–495. doi:10.1016/j.it.2005.07.004

    CAS  PubMed  Google Scholar 

  • Engelhardt B, Wolburg-Buchholz K, Wolburg H (2001) Involvement of the choroid plexus in central nervous system inflammation. Microsc Res Tech 52(1):112–129. doi:10.1002/1097-0029(20010101)52:1<112::AID-JEMT13>3.0.CO;2-5

    CAS  PubMed  Google Scholar 

  • Fallon J, Reid S, Kinyamu R, Opole I, Opole R, Baratta J, Korc M, Endo TL, Duong A, Nguyen G, Karkehabadhi M, Twardzik D, Patel S, Loughlin S (2000) In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brain. Proc Natl Acad Sci U S A 97(26):14686–14691. doi:10.1073/pnas.97.26.14686

    PubMed Central  CAS  PubMed  Google Scholar 

  • Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM (2002) B cells regulate autoimmunity by provision of IL-10. Nat Immunol 3(10):944–950. doi:10.1038/ni833

    CAS  PubMed  Google Scholar 

  • Fischer R, Maier O, Siegemund M, Wajant H, Scheurich P, Pfizenmaier K (2011) A TNF receptor 2 selective agonist rescues human neurons from oxidative stress-induced cell death. PLoS ONE 6(11):e27621. doi:10.1371/journal.pone.0027621

    PubMed Central  CAS  PubMed  Google Scholar 

  • Friese MA, Jakobsen KB, Friis L, Etzensperger R, Craner MJ, McMahon RM, Jensen LT, Huygelen V, Jones EY, Bell JI, Fugger L (2008) Opposing effects of HLA class I molecules in tuning autoreactive CD8+ T cells in multiple sclerosis. Nat Med 14(11):1227–1235. doi:10.1038/nm.1881

    CAS  PubMed  Google Scholar 

  • Gage FH (2000) Mammalian neural stem cells. Science 287(5457):1433–1438. doi:10.1126/science.287.5457.1433

    CAS  PubMed  Google Scholar 

  • Gebara E, Sultan S, Kocher-Braissant J, Toni N (2013) Adult hippocampal neurogenesis inversely correlates with microglia in conditions of voluntary running and aging. Front Neurosci 7:145. doi:10.3389/fnins.2013.00145

    PubMed Central  PubMed  Google Scholar 

  • Gong X, He X, Qi L, Zuo H, Xie Z (2006) Stromal cell derived factor-1 acutely promotes neural progenitor cell proliferation in vitro by a mechanism involving the ERK1/2 and PI-3K signal pathways. Cell Biol Int 30(5):466–471. doi:10.1016/j.cellbi.2006.01.007

    CAS  PubMed  Google Scholar 

  • Gould E, Tanapat P (1997) Lesion-induced proliferation of neuronal progenitors in the dentate gyrus of the adult rat. Neuroscience 80(2):427–436

    CAS  PubMed  Google Scholar 

  • Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, Fitzgerald KA, Latz E, Moore KJ, Golenbock DT (2008) The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol 9(8):857–865. doi:10.1038/ni.1636

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hanisch UK, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10(11):1387–1394. doi:10.1038/nn1997

    CAS  PubMed  Google Scholar 

  • Hermann A, Maisel M, Wegner F, Liebau S, Kim DW, Gerlach M, Schwarz J, Kim KS, Storch A (2006) Multipotent neural stem cells from the adult tegmentum with dopaminergic potential develop essential properties of functional neurons. Stem Cells 24(4):949–964. doi:10.1634/stemcells.2005-0192

    CAS  PubMed  Google Scholar 

  • Hickey WF (2001) Basic principles of immunological surveillance of the normal central nervous system. Glia 36(2):118–124

    CAS  PubMed  Google Scholar 

  • Hirano T, Taga T, Nakano N, Yasukawa K, Kashiwamura S, Shimizu K, Nakajima K, Pyun KH, Kishimoto T (1985) Purification to homogeneity and characterization of human B-cell differentiation factor (BCDF or BSFp-2). Proc Natl Acad Sci U S A 82(16):5490–5494

    PubMed Central  CAS  PubMed  Google Scholar 

  • Huang GJ, Smith AL, Gray DH, Cosgrove C, Singer BH, Edwards A, Sims S, Parent JM, Johnsen A, Mott R, Mathis D, Klenerman P, Benoist C, Flint J (2010) A genetic and functional relationship between T cells and cellular proliferation in the adult hippocampus. PLoS Biol 8(12):e1000561. doi:10.1371/journal.pbio.1000561

    PubMed Central  CAS  PubMed  Google Scholar 

  • Iadecola C, Anrather J (2011) The immunology of stroke: from mechanisms to translation. Nat Med 17(7):796–808. doi:10.1038/nm.2399

    PubMed Central  CAS  PubMed  Google Scholar 

  • Imitola J, Raddassi K, Park KI, Mueller FJ, Nieto M, Teng YD, Frenkel D, Li J, Sidman RL, Walsh CA, Snyder EY, Khoury SJ (2004) Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci U S A 101(52):18117–18122. doi:10.1073/pnas.0408258102

    PubMed Central  CAS  PubMed  Google Scholar 

  • 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 Off J Soc Neurosci 26(38):9703–9712. doi:10.1523/JNEUROSCI.2723-06.2006

    CAS  Google Scholar 

  • Jiang W, Gu W, Brannstrom T, Rosqvist R, Wester P (2001) Cortical neurogenesis in adult rats after transient middle cerebral artery occlusion. Stroke J Cereb Circ 32(5):1201–1207

    CAS  Google Scholar 

  • Jin K, Minami M, Lan JQ, Mao XO, Batteur S, Simon RP, Greenberg DA (2001) Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc Natl Acad Sci U S A 98(8):4710–4715. doi:10.1073/pnas.081011098

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jin K, Wang X, Xie L, Mao XO, Greenberg DA (2010) Transgenic ablation of doublecortin-expressing cells suppresses adult neurogenesis and worsens stroke outcome in mice. Proc Natl Acad Sci U S A 107(17):7993–7998. doi:10.1073/pnas.1000154107

    PubMed Central  CAS  PubMed  Google Scholar 

  • Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisen J (1999) Identification of a neural stem cell in the adult mammalian central nervous system. Cell 96(1):25–34

    CAS  PubMed  Google Scholar 

  • Kim SJ, Son TG, Kim K, Park HR, Mattson MP, Lee J (2007) Interferon-gamma promotes differentiation of neural progenitor cells via the JNK pathway. Neurochem Res 32(8):1399–1406. doi:10.1007/s11064-007-9323-z

    CAS  PubMed  Google Scholar 

  • Kleine TO, Benes L (2006) Immune surveillance of the human central nervous system (CNS): different migration pathways of immune cells through the blood-brain barrier and blood-cerebrospinal fluid barrier in healthy persons. Cytometry A J Int Soc Anal Cytol 69(3):147–151. doi:10.1002/cyto.a.20225

    Google Scholar 

  • Kohman RA, Rhodes JS (2013) Neurogenesis, inflammation and behavior. Brain Behav Immun 27(1):22–32. doi:10.1016/j.bbi.2012.09.003

    CAS  PubMed  Google Scholar 

  • 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):751–756. doi:10.1073/pnas.0708092105

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kooij G, van Horssen J, de Lange EC, Reijerkerk A, van der Pol SM, van Het Hof B, Drexhage J, Vennegoor A, Killestein J, Scheffer G, Oerlemans R, Scheper R, van der Valk P, Dijkstra CD, de Vries HE (2010) T lymphocytes impair P-glycoprotein function during neuroinflammation. J Autoimmun 34(4):416–425. doi:10.1016/j.jaut.2009.10.006

    CAS  PubMed  Google Scholar 

  • Krathwohl MD, Kaiser JL (2004) Chemokines promote quiescence and survival of human neural progenitor cells. Stem Cells 22(1):109–118. doi:10.1634/stemcells.22-1-109

    CAS  PubMed  Google Scholar 

  • Lee JM, Zipfel GJ, Choi DW (1999) The changing landscape of ischaemic brain injury mechanisms. Nature 399(6738 Suppl):A7–A14

    CAS  PubMed  Google Scholar 

  • Lee H, Kang JE, Lee JK, Bae JS, Jin HK (2013) Bone-marrow-derived mesenchymal stem cells promote proliferation and neuronal differentiation of Niemann-Pick type C mouse neural stem cells by upregulation and secretion of CCL2. Hum Gene Ther 24(7):655–669. doi:10.1089/hum.2013.001

    PubMed Central  CAS  PubMed  Google Scholar 

  • Leker RR, Shohami E (2002) Cerebral ischemia and trauma-different etiologies yet similar mechanisms: neuroprotective opportunities. Brain Res Brain Res Rev 39(1):55–73

    PubMed  Google Scholar 

  • Li X, Newbern JM, Wu Y, Morgan-Smith M, Zhong J, Charron J, Snider WD (2012) MEK is a key regulator of gliogenesis in the developing brain. Neuron 75(6):1035–1050. doi:10.1016/j.neuron.2012.08.031

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ling ZD, Potter ED, Lipton JW, Carvey PM (1998) Differentiation of mesencephalic progenitor cells into dopaminergic neurons by cytokines. Exp Neurol 149(2):411–423. doi:10.1006/exnr.1998.6715

    CAS  PubMed  Google Scholar 

  • Liu J, Solway K, Messing RO, Sharp FR (1998) Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils. J Neurosci Off J Soc Neurosci 18(19):7768–7778

    CAS  Google Scholar 

  • Liu YP, Lin HI, Tzeng SF (2005) Tumor necrosis factor-alpha and interleukin-18 modulate neuronal cell fate in embryonic neural progenitor culture. Brain Res 1054(2):152–158. doi:10.1016/j.brainres.2005.06.085

    CAS  PubMed  Google Scholar 

  • Magavi SS, Leavitt BR, Macklis JD (2000) Induction of neurogenesis in the neocortex of adult mice. Nature 405(6789):951–955. doi:10.1038/35016083

    CAS  PubMed  Google Scholar 

  • 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):1368–1385. doi:10.1111/j.1471-4159.2009.06548.x

    CAS  PubMed  Google Scholar 

  • Matsushita T, Matsuoka T, Ishizu T, Kikuchi H, Osoegawa M, Kawano Y, Mihara F, Ohyagi Y, Kira J (2008) Anterior periventricular linear lesions in optic-spinal multiple sclerosis: a combined neuroimaging and neuropathological study. Mult Scler 14(3):343–353. doi:10.1177/1352458507084085

    PubMed  Google Scholar 

  • Ming GL, Song H (2005) Adult neurogenesis in the mammalian central nervous system. Ann Rev Neurosci 28:223–250. doi:10.1146/annurev.neuro.28.051804.101459

    CAS  PubMed  Google Scholar 

  • Molyneaux KA, Zinszner H, Kunwar PS, Schaible K, Stebler J, Sunshine MJ, O’Brien W, Raz E, Littman D, Wylie C, Lehmann R (2003) The chemokine SDF1/CXCL12 and its receptor CXCR4 regulate mouse germ cell migration and survival. Development 130(18):4279–4286

    CAS  PubMed  Google Scholar 

  • Monje ML, Palmer T (2003) Radiation injury and neurogenesis. Curr Opin Neurol 16(2):129–134. doi:10.1097/01.wco.0000063772.81810.b7

    PubMed  Google Scholar 

  • Monje ML, Toda H, Palmer TD (2003) Inflammatory blockade restores adult hippocampal neurogenesis. Science 302(5651):1760–1765. doi:10.1126/science.1088417

    CAS  PubMed  Google Scholar 

  • Morgan SC, Taylor DL, Pocock JM (2004) Microglia release activators of neuronal proliferation mediated by activation of mitogen-activated protein kinase, phosphatidylinositol-3-kinase/Akt and delta-Notch signalling cascades. J Neurochem 90(1):89–101. doi:10.1111/j.1471-4159.2004.02461.x

    CAS  PubMed  Google Scholar 

  • Nakatomi H, Kuriu T, Okabe S, Yamamoto S, Hatano O, Kawahara N, Tamura A, Kirino T, Nakafuku M (2002) Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors. Cell 110(4):429–441

    CAS  PubMed  Google Scholar 

  • Namihira M, Nakashima K (2013) Mechanisms of astrocytogenesis in the mammalian brain. Curr Opin Neurobiol 23(6):921–927. doi:10.1016/j.conb.2013.06.002

    CAS  PubMed  Google Scholar 

  • Neher JJ, Emmrich JV, Fricker M, Mander PK, Thery C, Brown GC (2013) Phagocytosis executes delayed neuronal death after focal brain ischemia. Proc Natl Acad Sci U S A 110(43):E4098–E4107. doi:10.1073/pnas.1308679110

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ni HT, Hu S, Sheng WS, Olson JM, Cheeran MC, Chan AS, Lokensgard JR, Peterson PK (2004) High-level expression of functional chemokine receptor CXCR4 on human neural precursor cells. Brain Res Dev Brain Res 152(2):159–169. doi:10.1016/j.devbrainres.2004.06.015

    CAS  PubMed  Google Scholar 

  • Ohira K (2011) Injury-induced neurogenesis in the mammalian forebrain. Cell Mol Life Sci 68(10):1645–1656. doi:10.1007/s00018-010-0552-y

    CAS  PubMed  Google Scholar 

  • 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):1046–1061. doi:10.1002/glia.20828

    PubMed  Google Scholar 

  • Parent JM, Vexler ZS, Gong C, Derugin N, Ferriero DM (2002) Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol 52(6):802–813. doi:10.1002/ana.10393

    PubMed  Google Scholar 

  • Peng H, Huang Y, Rose J, Erichsen D, Herek S, Fujii N, Tamamura H, Zheng J (2004) Stromal cell-derived factor 1-mediated CXCR4 signaling in rat and human cortical neural progenitor cells. J Neurosci Res 76(1):35–50. doi:10.1002/jnr.20045

    CAS  PubMed  Google Scholar 

  • Richardson RM, Sun D, Bullock MR (2007) Neurogenesis after traumatic brain injury. Neurosurg Clin N Am 18(1):169–181. doi:10.1016/j.nec.2006.10.007, xi

    PubMed  Google Scholar 

  • Saino O, Taguchi A, Nakagomi T, Nakano-Doi A, Kashiwamura S, Doe N, Nakagomi N, Soma T, Yoshikawa H, Stern DM, Okamura H, Matsuyama T (2010) Immunodeficiency reduces neural stem/progenitor cell apoptosis and enhances neurogenesis in the cerebral cortex after stroke. J Neurosci Res 88(11):2385–2397. doi:10.1002/jnr.22410

    CAS  PubMed  Google Scholar 

  • Schwamborn J, Lindecke A, Elvers M, Horejschi V, Kerick M, Rafigh M, Pfeiffer J, Prullage M, Kaltschmidt B, Kaltschmidt C (2003) Microarray analysis of tumor necrosis factor alpha induced gene expression in U373 human glioblastoma cells. BMC Genomics 4(1):46. doi:10.1186/1471-2164-4-46

    PubMed Central  PubMed  Google Scholar 

  • Schwartz M, Shechter R (2010) Protective autoimmunity functions by intracranial immunosurveillance to support the mind: the missing link between health and disease. Mol Psychiatry 15(4):342–354. doi:10.1038/mp.2010.31

    CAS  PubMed  Google Scholar 

  • Shaked I, Tchoresh D, Gersner R, Meiri G, Mordechai S, Xiao X, Hart RP, Schwartz M (2005) Protective autoimmunity: interferon-gamma enables microglia to remove glutamate without evoking inflammatory mediators. J Neurochem 92(5):997–1009. doi:10.1111/j.1471-4159.2004.02954.x

    CAS  PubMed  Google Scholar 

  • Song H, Stevens CF, Gage FH (2002) Astroglia induce neurogenesis from adult neural stem cells. Nature 417(6884):39–44. doi:10.1038/417039a

    CAS  PubMed  Google Scholar 

  • Sparkman NL, Johnson RW (2008) Neuroinflammation associated with aging sensitizes the brain to the effects of infection or stress. Neuroimmunomodulation 15(4–6):323–330. doi:10.1159/000156474

    PubMed Central  CAS  PubMed  Google Scholar 

  • Speisman RB, Kumar A, Rani A, Foster TC, Ormerod BK (2013) Daily exercise improves memory, stimulates hippocampal neurogenesis and modulates immune and neuroimmune cytokines in aging rats. Brain Behav Immun 28:25–43. doi:10.1016/j.bbi.2012.09.013

    PubMed Central  CAS  PubMed  Google Scholar 

  • St-John WM (1998) Neurogenesis of patterns of automatic ventilatory activity. Prog Neurobiol 56(1):97–117

    CAS  PubMed  Google Scholar 

  • Sultan S, Gebara E, Toni N (2013) Doxycycline increases neurogenesis and reduces microglia in the adult hippocampus. Front Neurosci 7:131. doi:10.3389/fnins.2013.00131

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sun C, Sun H, Wu S, Lee CC, Akamatsu Y, Wang RK, Kernie SG, Liu J (2013) Conditional ablation of neuroprogenitor cells in adult mice impedes recovery of poststroke cognitive function and reduces synaptic connectivity in the perforant pathway. J Neurosci Off J Soc Neurosci 33(44):17314–17325. doi:10.1523/JNEUROSCI.2129-13.2013

    CAS  Google Scholar 

  • Taga T, Fukuda S (2005) Role of IL-6 in the neural stem cell differentiation. Clin Rev Allergy Immunol 28(3):249–256. doi:10.1385/CRIAI:28:3:249

    CAS  PubMed  Google Scholar 

  • Tang H, Wang Y, Xie L, Mao X, Won SJ, Galvan V, Jin K (2009) Effect of neural precursor proliferation level on neurogenesis in rat brain during aging and after focal ischemia. Neurobiol Aging 30(2):299–308. doi:10.1016/j.neurobiolaging.2007.06.004

    PubMed Central  PubMed  Google Scholar 

  • Temple S (2001) The development of neural stem cells. Nature 414(6859):112–117. doi:10.1038/35102174

    CAS  PubMed  Google Scholar 

  • Vadasz Z, Haj T, Kessel A, Toubi E (2013) B-regulatory cells in autoimmunity and immune mediated inflammation. FEBS Lett 587(13):2074–2078. doi:10.1016/j.febslet.2013.05.023

    CAS  PubMed  Google Scholar 

  • 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 Off J Soc Neurosci 22(2):486–492

    CAS  Google Scholar 

  • Voloboueva LA, Giffard RG (2011) Inflammation, mitochondria, and the inhibition of adult neurogenesis. J Neurosci Res 89(12):1989–1996. doi:10.1002/jnr.22768

    PubMed Central  CAS  PubMed  Google Scholar 

  • Walsh JT, Kipnis J (2011) Regulatory T cells in CNS injury: the simple, the complex and the confused. Trends Mol Med 17(10):541–547. doi:10.1016/j.molmed.2011.05.012

    PubMed Central  CAS  PubMed  Google Scholar 

  • Walter J, Honsek SD, Illes S, Wellen JM, Hartung HP, Rose CR, Dihne M (2011) A new role for interferon gamma in neural stem/precursor cell dysregulation. Mol Neurodegener 6:18. doi:10.1186/1750-1326-6-18

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wang Q, Tang XN, Yenari MA (2007) The inflammatory response in stroke. J Neuroimmunol 184(1–2):53–68. doi:10.1016/j.jneuroim.2006.11.014

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wang W, Bu B, Xie M, Zhang M, Yu Z, Tao D (2009) Neural cell cycle dysregulation and central nervous system diseases. Prog Neurobiol 89(1):1–17. doi:10.1016/j.pneurobio.2009.01.007

    CAS  PubMed  Google Scholar 

  • Wang T, Lee MH, Johnson T, Allie R, Hu L, Calabresi PA, Nath A (2010) Activated T-cells inhibit neurogenesis by releasing granzyme B: rescue by Kv1.3 blockers. J Neurosci Off J Soc Neurosci 30(14):5020–5027. doi:10.1523/JNEUROSCI.0311-10.2010

    CAS  Google Scholar 

  • Wang FW, Hao HB, Zhao SD, Zhang YM, Liu Q, Liu HJ, Liu SM, Yuan QH, Bing LJ, Ling EA, Hao AJ (2011) Roles of activated astrocyte in neural stem cell proliferation and differentiation. Stem Cell Res 7(1):41–53. doi:10.1016/j.scr.2011.03.004

    CAS  PubMed  Google Scholar 

  • 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):381–387. doi:10.1078/0171-9335-00403

    CAS  PubMed  Google Scholar 

  • Winner B, Kohl Z, Gage FH (2011) Neurodegenerative disease and adult neurogenesis. Eur J NeuroSci 33(6):1139–1151. doi:10.1111/j.1460-9568.2011.07613.x

    PubMed  Google Scholar 

  • Wolf SD, Dittel BN, Hardardottir F, Janeway CA Jr (1996) Experimental autoimmune encephalomyelitis induction in genetically B cell-deficient mice. J Exp Med 184(6):2271–2278

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wolf SA, Steiner B, Akpinarli A, Kammertoens T, Nassenstein C, Braun A, Blankenstein T, Kempermann G (2009a) CD4-positive T lymphocytes provide a neuroimmunological link in the control of adult hippocampal neurogenesis. J Immunol 182(7):3979–3984. doi:10.4049/jimmunol.0801218

    CAS  PubMed  Google Scholar 

  • Wolf SA, Steiner B, Wengner A, Lipp M, Kammertoens T, Kempermann G (2009b) Adaptive peripheral immune response increases proliferation of neural precursor cells in the adult hippocampus. FASEB J Off Publ Fed Am Soc Exp Biol 23(9):3121–3128. doi:10.1096/fj.08-113944

    CAS  Google Scholar 

  • 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):171–177. doi:10.1016/j.expneurol.2004.01.009

    CAS  PubMed  Google Scholar 

  • Wu Y, Peng H, Cui M, Whitney NP, Huang Y, Zheng JC (2009) CXCL12 increases human neural progenitor cell proliferation through Akt-1/FOXO3a signaling pathway. J Neurochem 109(4):1157–1167. doi:10.1111/j.1471-4159.2009.06043.x

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wu MD, Hein AM, Moravan MJ, Shaftel SS, Olschowka JA, O’Banion MK (2012a) Adult murine hippocampal neurogenesis is inhibited by sustained IL-1beta and not rescued by voluntary running. Brain Behav Immun 26(2):292–300. doi:10.1016/j.bbi.2011.09.012

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wu Y, Chen Q, Peng H, Dou H, Zhou Y, Huang Y, Zheng JC (2012b) Directed migration of human neural progenitor cells to interleukin-1beta is promoted by chemokines stromal cell-derived factor-1 and monocyte chemotactic factor-1 in mouse brains. Transl Neurodegener 1(1):15. doi:10.1186/2047-9158-1-15

    PubMed Central  CAS  PubMed  Google Scholar 

  • Xiong X, Barreto GE, Xu L, Ouyang YB, Xie X, Giffard RG (2011) Increased brain injury and worsened neurological outcome in interleukin-4 knockout mice after transient focal cerebral ischemia. Stroke J Cereb Circ 42(7):2026–2032. doi:10.1161/STROKEAHA.110.593772

    Google Scholar 

  • Yamamoto S, Nagao M, Sugimori M, Kosako H, Nakatomi H, Yamamoto N, Takebayashi H, Nabeshima Y, Kitamura T, Weinmaster G, Nakamura K, Nakafuku M (2001) Transcription factor expression and Notch-dependent regulation of neural progenitors in the adult rat spinal cord. J Neurosci Off J Soc Neurosci 21(24):9814–9823

    CAS  Google Scholar 

  • Ying W (2007) NAD+ and NADH in brain functions, brain diseases and brain aging. Front Biosci J Virtual Libr 12:1863–1888

    CAS  Google Scholar 

  • Zhao M, Momma S, Delfani K, Carlen M, Cassidy RM, Johansson CB, Brismar H, Shupliakov O, Frisen J, Janson AM (2003) Evidence for neurogenesis in the adult mammalian substantia nigra. Proc Natl Acad Sci U S A 100(13):7925–7930. doi:10.1073/pnas.1131955100

    PubMed Central  CAS  PubMed  Google Scholar 

  • Zhu B, Xu D, Deng X, Chen Q, Huang Y, Peng H, Li Y, Jia B, Thoreson WB, Ding W, Ding J, Zhao L, Wang Y, Wavrin KL, Duan S, Zheng J (2012) CXCL12 enhances human neural progenitor cell survival through a CXCR7- and CXCR4-mediated endocytotic signaling pathway. Stem Cells 30(11):2571–2583. doi:10.1002/stem.1239

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ziebell JM, Morganti-Kossmann MC (2010) Involvement of pro- and anti-inflammatory cytokines and chemokines in the pathophysiology of traumatic brain injury. Neurother J Am Soc Exp Neurother 7(1):22–30. doi:10.1016/j.nurt.2009.10.016

    CAS  Google Scholar 

  • 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):471–478. doi:10.1016/j.molmed.2008.09.004

    CAS  PubMed  Google Scholar 

  • 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):268–275. doi:10.1038/nn1629

    CAS  PubMed  Google Scholar 

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Acknowledgments

This work was partially supported by National Institute of Health (NIH) grants AG21980 and NS057186 (KJ).

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  1. Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX, 76107, USA

    Brian Wang & Kunlin Jin

  2. Institute of Aging and Alzheimer’s Disease Research, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA

    Brian Wang & Kunlin Jin

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Correspondence to Kunlin Jin.

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Wang, B., Jin, K. Current perspectives on the link between neuroinflammation and neurogenesis. Metab Brain Dis 30, 355–365 (2015). https://doi.org/10.1007/s11011-014-9523-6

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