Journal of Neuroimmune Pharmacology

, Volume 2, Issue 3, pp 236–242

Endogenous Neural Stem Cells in the Adult Brain

Invited Review

Abstract

Despite progress in our understanding molecular mechanisms of neuronal cell death in many central nervous system (CNS) diseases, widely effective treatments remain elusive. Recent studies have shown that neural stem cells (NSCs) are present in the subventricular zone (SVZ) lining the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) in adult mouse, rat, nonhuman primate, and human brain. Newly generated cells in the SGZ can differentiate into mature, functional neurons and integrate into the DG as granule cells, which are involved in memory formation. In addition, many CNS diseases can stimulate the proliferation of neuronal stem/progenitor cells located in the SVZ and SGZ of the adult rodent brain, and the resulting newborn cells migrate into damaged brain regions, where they express mature neuronal markers. Therefore, it might be possible for damaged cells to be replaced from endogenous neural stem cell pools. However, the capacity of self-repair is obviously not enough. Proliferation, migration, and neuronal differentiation of endogenous NSCs could be manipulated by pharmaceutical tools to reach the adequate benefits for the treatment of CNS diseases.

Keywords

stem cells brain adult endogenous 

References

  1. Aimone JB, Wiles J, Gage FH (2006) Potential role for adult neurogenesis in the encoding of time in new memories. Nat Neurosci 9:723–727.PubMedCrossRefGoogle Scholar
  2. Alonso G, Prieto M, Chauvet N (1999) Tangential migration of young neurons arising from the subventricular zone of adult rats is impaired by surgical lesions passing through their natural migratory pathway. J Comp Neurol 405:508–528.PubMedCrossRefGoogle Scholar
  3. Barker CF, Billingham RE (1977) Immunologically privileged sites. Adv Immunol 25:1–54.PubMedCrossRefGoogle Scholar
  4. Bayer SA (1985) Neuron production in the hippocampus and olfactory bulb of the adult rat brain: addition or replacement? Ann N Y Acad Sci 457:163–172.PubMedCrossRefGoogle Scholar
  5. Binder LI, Frankfurter A, Kim H, Caceres A, Payne MR, Rebhun LI (1984) Heterogeneity of microtubule-associated protein 2 during rat brain development. Proc Natl Acad Sci U S A 81:5613–5617.PubMedCrossRefGoogle Scholar
  6. Bonfanti L, Theodosis DT (1994) Expression of polysialylated neural cell adhesion molecule by proliferating cells in the subependymal layer of the adult rat, in its rostral extension and in the olfactory bulb. Neuroscience 62:291–305.PubMedCrossRefGoogle Scholar
  7. Cameron HA, Hazel TG, McKay RD (1998) Regulation of neurogenesis by growth factors and neurotransmitters. J Neurobiol 36:287–306.PubMedCrossRefGoogle Scholar
  8. Cameron HA, Woolley CS, McEwen BS, Gould E (1993) Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience 56:337–344.PubMedCrossRefGoogle Scholar
  9. Clevers H (2005) Stem cells, asymmetric division and cancer. Nat Genet 37:1027–1028.PubMedCrossRefGoogle Scholar
  10. Craig CG, Tropepe V, Morshead CM, Reynolds BA, Weiss S, van der Kooy D (1996) In vivo growth factor expansion of endogenous subependymal neural precursor cell populations in the adult mouse brain. J Neurosci 16:2649–2658.PubMedGoogle Scholar
  11. 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 315:1243–1249.PubMedCrossRefGoogle Scholar
  12. Debus E, Weber K, Osborn M (1983) Monoclonal antibodies specific for glial fibrillary acidic (GFA) protein and for each of the neurofilament triplet polypeptides. Differentiation 25:193–203.PubMedCrossRefGoogle Scholar
  13. des Portes V, Francis F, Pinard JM, Desguerre I, Moutard ML, Snoeck I, Meiners LC, Capron F, Cusmai R, Ricci S, Motte J, Echenne B, Ponsot G, Dulac O, Chelly J, Beldjord C (1998) Doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH). Hum Mol Genet 7:1063–1070.PubMedCrossRefGoogle Scholar
  14. Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH (1998) Neurogenesis in the adult human hippocampus. Nat Med 4:1313–1317.PubMedCrossRefGoogle Scholar
  15. Fanarraga ML, Avila J, Zabala JC (1999) Expression of unphosphorylated class III beta-tubulin isotype in neuroepithelial cells demonstrates neuroblast commitment and differentiation. Eur J Neurosci 11:516–527.PubMedCrossRefGoogle Scholar
  16. Francis F, Koulakoff A, Boucher D, Chafey P, Schaar B, Vinet MC, Friocourt G, McDonnell N, Reiner O, Kahn A, McConnell SK, Berwald-Netter Y, Denoulet P, Chelly J (1999) Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron 23:247–256.PubMedCrossRefGoogle Scholar
  17. Ge S, Goh EL, Sailor KA, Kitabatake Y, Ming GL, Song H (2006) GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature 439:589–593.PubMedCrossRefGoogle Scholar
  18. Gould E, Beylin A, Tanapat P, Reeves A, Shors TJ (1999) Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci 2:260–265.PubMedCrossRefGoogle Scholar
  19. Gould E, Cameron HA, Daniels DC, Woolley CS, McEwen BS (1992) Adrenal hormones suppress cell division in the adult rat dentate gyrus. J Neurosci 12:3642–3650.PubMedGoogle Scholar
  20. Gould E, McEwen BS, Tanapat P, Galea LAM, Fuchs E (1997) Neurogenesis in the Dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J Neurosci 17:2492–2498.PubMedGoogle Scholar
  21. Gutig R, Sompolinsky H (2006) The tempotron: a neuron that learns spike timing-based decisions. Nat Neurosci 9:420–428.PubMedCrossRefGoogle Scholar
  22. Jin K, LaFevre-Bernt M, Sun Y, Chen S, Gafni J, Crippen D, Logvinova A, Ross CA, Greenberg DA, Ellerby LM (2005) FGF-2 promotes neurogenesis and neuroprotection and prolongs survival in a transgenic mouse model of Huntington’s disease. Proc Natl Acad Sci U S A 102:18189–18194.PubMedCrossRefGoogle Scholar
  23. 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 98:4710–4715.PubMedCrossRefGoogle Scholar
  24. Jin K, Peel AL, Mao XO, Xie L, Cottrell BA, Henshall DC, Greenberg DA (2004) Increased hippocampal neurogenesis in Alzheimer’s disease. Proc Natl Acad Sci U S A 101:343–347.PubMedCrossRefGoogle Scholar
  25. Jin K, Wang X, Xie L, Mao XO, Zhu W, Wang Y, Shen J, Mao Y, Banwait S, Greenberg DA (2006a) Evidence for stroke-induced neurogenesis in the human brain. Proc Natl Acad Sci U S A 103:13198–13202.CrossRefGoogle Scholar
  26. Jin K, Xie L, Mao XO, Greenberg DA (2006b) Alzheimer’s disease drugs promote neurogenesis. Brain Res 1085:183–188.CrossRefGoogle Scholar
  27. Kaneko Y, Sakakibara S, Imai T, Suzuki A, Nakamura Y, Sawamoto K, Ogawa Y, Toyama Y, Miyata T, Okano H (2000) Musashi1: an evolutionally conserved marker for CNS progenitor cells including neural stem cells. Dev Neurosci 22:139–153.PubMedCrossRefGoogle Scholar
  28. Kempermann G, Gast D, Gage FH (2002) Neuroplasticity in old age: sustained fivefold induction of hippocampal neurogenesis by long-term environmental enrichment. Ann Neurol 52:135–143.PubMedCrossRefGoogle Scholar
  29. Kirschenbaum B, Doetsch F, Lois C, Alvarez-Buylla A (1999) Adult subventricular zone neuronal precursors continue to proliferate and migrate in the absence of the olfactory bulb. J Neurosci 19:2171–2180.PubMedGoogle Scholar
  30. Kirschenbaum B, Nedergaard M, Preuss A, Barami K, Fraser RA, Goldman SA (1994) In vitro neuronal production and differentiation by precursor cells derived from the adult human forebrain. Cereb Cortex 4:576–589.PubMedCrossRefGoogle Scholar
  31. Kuhn HG, Winkler J, Kempermann G, Thal LJ, Gage FH (1997) Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain. J Neurosci 17:5820–5829.PubMedGoogle Scholar
  32. Lillien L, Cepko C (1992) Control of proliferation in the retina: temporal changes in responsiveness to FGF and TGF alpha. Development 115:253–266.PubMedGoogle Scholar
  33. Lin X, Bulleit RF (1997) Insulin-like growth factor I (IGF-I) is a critical trophic factor for developing cerebellar granule cells. Brain Res Dev Brain Res 99:234–242.PubMedCrossRefGoogle Scholar
  34. Lindvall O, Kokaia Z (2006) Stem cells for the treatment of neurological disorders. Nature 441:1094–1096.PubMedCrossRefGoogle Scholar
  35. Lois C, Garcia-Verdugo JM, Alvarez-Buylla A (1996) Chain migration of neuronal precursors. Science 271:978–981.PubMedCrossRefGoogle Scholar
  36. Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20:9104–9110.PubMedGoogle Scholar
  37. Marusich MF, Furneaux HM, Henion PD, Weston JA (1994) Hu neuronal proteins are expressed in proliferating neurogenic cells. J Neurobiol 25:143–155.PubMedCrossRefGoogle Scholar
  38. McDermott KW, Lantos PL (1991) Distribution and fine structural analysis of undifferentiated cells in the primate subependymal layer. J Anat 178:45–63.PubMedGoogle Scholar
  39. Mullen RJ, Buck CR, Smith AM (1992) NeuN, a neuronal specific nuclear protein in vertebrates. Development 116:201–211.PubMedGoogle Scholar
  40. Nadareishvili Z, Hallenbeck J (2003) Neuronal regeneration after stroke. N Engl J Med 348:2355–2356.PubMedCrossRefGoogle Scholar
  41. Pencea V, Bingaman KD, Wiegand SJ, Luskin MB (2001) Infusion of brain-derived neurotrophic factor into the lateral ventricle of the adult rat leads to new neurons in the parenchyma of the striatum, septum, thalamus, and hypothalamus. J Neurosci 21:6706–6717.PubMedGoogle Scholar
  42. Raber J, Fan Y, Matsumori Y, Liu Z, Weinstein PR, Fike JR, Liu J (2004) Irradiation attenuates neurogenesis and exacerbates ischemia-induced deficits. Ann Neurol 55:381–389.PubMedCrossRefGoogle Scholar
  43. Ranscht B, Clapshaw PA, Price J, Noble M, Seifert W (1982) Development of oligodendrocytes and Schwann cells studied with a monoclonal antibody against galactocerebroside. Proc Natl Acad Sci U S A 79:2709–2713.PubMedCrossRefGoogle Scholar
  44. Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–1710.PubMedCrossRefGoogle Scholar
  45. Rossi C, Angelucci A, Costantin L, Braschi C, Mazzantini M, Babbini F, Fabbri ME, Tessarollo L, Maffei L, Berardi N, Caleo M (2006) Brain-derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment. Eur J Neurosci 24:1850–1856.PubMedCrossRefGoogle Scholar
  46. Rousselot P, Lois C, Alvarez-Buylla A (1995) Embryonic (PSA) N-CAM reveals chains of migrating neuroblasts between the lateral ventricle and the olfactory bulb of adult mice. J Comp Neurol 351:51–61.PubMedCrossRefGoogle Scholar
  47. Sanai N, Tramontin AD, Quinones-Hinojosa A, Barbaro NM, Gupta N, Kunwar S, Lawton MT, McDermott MW, Parsa AT, Manuel-Garcia Verdugo J, Berger MS, Alvarez-Buylla A (2004) Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 427:740–744.PubMedCrossRefGoogle Scholar
  48. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R (2003) Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 301:805–809.PubMedCrossRefGoogle Scholar
  49. Sawamoto K, Nakao N, Kakishita K, Ogawa Y, Toyama Y, Yamamoto A, Yamaguchi M, Mori K, Goldman SA, Itakura T, Okano H (2001) Generation of dopaminergic neurons in the adult brain from mesencephalic precursor cells labeled with a nestin-GFP transgene. J Neurosci 21:3895–3903.PubMedGoogle Scholar
  50. Shors TJ, Miesegaes G, Beylin A, Zhao M, Rydel T, Gould E (2001) Neurogenesis in the adult is involved in the formation of trace memories. Nature 410:372–376.PubMedCrossRefGoogle Scholar
  51. Song HJ, Stevens CF, Gage FH (2002) Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons. Nat Neurosci 5:438–445.PubMedGoogle Scholar
  52. Suzuki M, Nelson AD, Eickstaedt JB, Wallace K, Wright LS, Svendsen CN (2006) Glutamate enhances proliferation and neurogenesis in human neural progenitor cell cultures derived from the fetal cortex. Eur J Neurosci 24:645–653.PubMedCrossRefGoogle Scholar
  53. Taupin P, Ray J, Fischer WH, Suhr ST, Hakansson K, Grubb A, Gage FH (2000) FGF-2-responsive neural stem cell proliferation requires CCg, a novel autocrine/paracrine cofactor. Neuron 28:385–397.PubMedCrossRefGoogle Scholar
  54. Wagner JP, Black IB, DiCicco-Bloom E (1999) Stimulation of neonatal and adult brain neurogenesis by subcutaneous injection of basic fibroblast growth factor. J Neurosci 19:6006–6016.PubMedGoogle Scholar
  55. Walker TL, Yasuda T, Adams DJ, Bartlett PF (2007) The doublecortin-expressing population in the developing and adult brain contains multipotential precursors in addition to neuronal-lineage cells. J Neurosci 27:3734–3742.PubMedCrossRefGoogle Scholar
  56. Yoshimura S, Takagi Y, Harada J, Teramoto T, Thomas SS, Waeber C, Bakowska JC, Breakefield XO, Moskowitz MA (2001) FGF-2 regulation of neurogenesis in adult hippocampus after brain injury. Proc Natl Acad Sci U S A 98:5874–5879.PubMedCrossRefGoogle Scholar
  57. Zhang R, LeTourneau Y, Gregg SR, Wang Y, Toh Y, Robin AM, Gang Zhang Z, Chopp M (2007) Neuroblast division during migration toward the ischemic striatum: a study of dynamic migratory and proliferative characteristics of neuroblasts from the subventricular zone. J Neurosci 27:3157–3162.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Buck Institute for Age ResearchNovatoUSA

Personalised recommendations