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Microenvironmental elements supporting adult hippocampal neurogenesis

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Abstract

Neurogenesis continues into adulthood in two distinct regions, the subventricular zone of the forebrain and the subgranular zone of the dentate gyrus. Transplantation experiments have suggested that the two neurogenic regions have a special microenvironment to support the proliferation and differentiation of stem or progenitor cells. As the candidates of the microenvironment, three elements have so far been proposed: (i) astrocytes; (ii) polysialyl neural cell adhesion molecule (PSA-NCAM)-expressing immature neurons; and (iii) blood vessels. In the early developmental process of neurogenesis, newly born cells make clusters within the neurogenic regions and the clusters are found to interact structurally with astrocytes, polysialic acidexpressing immature cells, endothelium and extravascular basal laminae of blood vessels. Furthermore, recent reports have shown that astrocytes support the proliferation and differentiation of stem cells in vitro. These results suggest that these microenvironmental elements contribute to the cell proliferation and differentiation of stem or progenitor cells. However, it remains to be determined how the microenvironmental elements support adult neurogenesis functionally and coordinate with each other.

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References

  • 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, 433–57.

    Article  PubMed  CAS  Google Scholar 

  • Altman J, Das GD (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124, 319–35.

    Article  PubMed  CAS  Google Scholar 

  • Alvarez-Buylla A, Buskirk RD, Nottebohm F (1987) Monoclonal antibody reveals radial glia in adult avian brain. J Comp Neurol 246, 159–70.

    Article  Google Scholar 

  • Alvarez-Buylla A, Garcia-Verdugo JM (2002) Neurogenesis in adult subventricular zone. J Neurosci 22, 629–34.

    PubMed  CAS  Google Scholar 

  • Alvarez-Buylla A, Seri B, Doetsch F (2002) Identification of neural stem cells in the adult vertebrate brain. Brain Res Bull 57, 751–8.

    Article  PubMed  Google Scholar 

  • Bayer SA (1983) 3H-Thymidine-radiographic studies of neurogenesis in the rat olfactory bulb. Exp Brain Res 50, 329–40.

    Article  PubMed  CAS  Google Scholar 

  • Bayer SA, Yackel JW, Puri PS (1982) Neurons in the rat dentate gyrus granular layer substantially increase during juvenile and adult life. Science 216, 890–2.

    Article  PubMed  CAS  Google Scholar 

  • Biro S, Yu ZX, Fu YM, Smale G et al. (1994) Expression and subcellular distribution of basic fibroblast growth factor are regulated during migration of endothelial cells. Circ Res 74, 485–94.

    PubMed  CAS  Google Scholar 

  • Bittman K, Owens DF, Kriegstein AR, LoTurco JJ (1997) Cell coupling and uncoupling in the ventricular zone of developing neocortex. J Neurosci 17, 7037–44.

    PubMed  CAS  Google Scholar 

  • 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, 337–44.

    Article  PubMed  CAS  Google Scholar 

  • Campos LS, Duarte AJ, Branco T, Henrique D (2001) mDll1 and mDI13 expression in the developing mouse brain: Role in the establishment of the early cortex. J Neurosci Res 64, 590–8.

    Article  PubMed  CAS  Google Scholar 

  • Doetsch F, Alvarez-Buylla A (1996) Network of tangential pathways for neuronal migration in adult mammalian brain. Proc Natl Acad Sci USA 93, 14 895–900.

    Google Scholar 

  • Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A (1999) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97, 703–16.

    Article  PubMed  CAS  Google Scholar 

  • Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A (1997) Cellular composition and three-dimensional organization of the sub-ventricular germinal zone in the adult mammalian brain. J Neurosci 17, 5046–61.

    PubMed  CAS  Google Scholar 

  • Du Y, Dreyfus CF (2002) Oligodendrocytes as providers of growth factors. J Neurosci Res 68, 647–54.

    Article  PubMed  CAS  Google Scholar 

  • Eckenhoff MF, Rakic P (1984) Radial organization of the hippoc-ampal dentate gyrus: A Golgi, ultrastructural, and immunocytochemical analysis in the developing Rhesus monkey. J Comp Neurol 223, 1–21.

    Article  PubMed  CAS  Google Scholar 

  • Eriksson PS, Perfilieva E, Bjork-Eriksson T et al. (1998) Neurogenesis in the adult human hippocampus. Nat Med 4, 1313–17.

    Article  PubMed  CAS  Google Scholar 

  • Fricker RA, Carpenter MK, Winkler C, Greco C, Gates MA, Bjorklund A (1999) Sitespecific migration and neuronal differentiation of human neural progenitor cells after transplantation in the adult rat brain. J Neurosci 19, 5990–6005.

    PubMed  CAS  Google Scholar 

  • Fuxe K, Chadi G, Tinner B, Agnati LF, Pettersson R, David G (1994) On the regional distribution of heparan sulfate proteoglycan immunoreactivity in the rat brain. Brain Res 636, 131–8.

    Article  PubMed  CAS  Google Scholar 

  • Gaiano N, Nye JS, Fishell G (2000) Radial glial identity is promoted by Notch1 signaling in the murine forebrain. Neuron 26, 395–404.

    Article  PubMed  CAS  Google Scholar 

  • Gould E, Gross CG (2002) Neurogenesis in adult mammals: Some progress and problems. J Neurosci 22, 619–23.

    PubMed  CAS  Google Scholar 

  • Gould E, McEwen BS, Tanapat P, Galea LA, 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, 2492–8.

    PubMed  CAS  Google Scholar 

  • Gregg CT, Chojnacki AK, Weiss S (2002) Radial glial cells as neuronal precursors: The next generation? J Neurosci Res 69, 708–13.

    Article  PubMed  CAS  Google Scholar 

  • Gross CG (2000) Neurogenesis in the adult brain: Death of a dogma. Nat Rev Neurosci 1, 67–73.

    Article  PubMed  CAS  Google Scholar 

  • Grothe C, Meisinger C, Claus P (2001) In vivo expression and localization of the fibroblast growth factor system in the intact and lesioned rat peripheral nerve and spinal ganglia. J Comp Neurol 434, 342–57.

    Article  PubMed  CAS  Google Scholar 

  • Hartmann D, Sievers J, Pehlemann FW, Berry M (1992) Destruction of meningeal cells over the medial cerebral hernisphere of newborn hamsters prevents the formation of the infrapyramidal blade of the dentate gyrus. J Comp Neurol 320, 33–61.

    Article  PubMed  CAS  Google Scholar 

  • Horner PJ, Power AE, Kempermann G et al. (2000) Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord. J Neurosci 20, 2218–28.

    PubMed  CAS  Google Scholar 

  • Irvin DK, Zurcher SD, Nguyen T, Weininaster G, Komblum HI (2001) Expression patterns of Notch1, Notch2, and Notch3 suggest multiple functional roles for the Notch-DSL signaling system during brain development. J Comp Neurol 436, 167–81.

    Article  PubMed  CAS  Google Scholar 

  • Jin K, Zhu Y, Sun Y, Mao XO, Xie L, Greenberg DA (2002) Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci USA 99, 11 946–50.

    Article  Google Scholar 

  • Kalman M, Hajos F (1989) Distribution of glial fibrillary acidic protein (GFAP) immunoreactive astrocytes in the rat brain. Exp Brain Res 78, 147–63.

    Article  PubMed  CAS  Google Scholar 

  • Kaplan MS, Hinds JW (1977) Neurogenesis in the adult rat: Electron microscopic analysis of light radioautographs. Science 197, 1092–4.

    Article  PubMed  CAS  Google Scholar 

  • Kaplan MS, McNelly NA, Hinds JW (1985) Population dynamics of adult-formed granule neurons of the rat olfactory bulb. J Comp Neurol 239, 117–25.

    Article  PubMed  CAS  Google Scholar 

  • Kehl U, Fairbanks CA, Laughlin TM, Wilcox GL (1997) Neurogenesis in postnatal rat spinal cord: A study in primary culture. Science 276, 586–9.

    Article  PubMed  CAS  Google Scholar 

  • Kiss JZ, Troncoso E, Djebbara Z, Vutskits L, Muller D (2001) The role of neural cell adhesion molecules in plasticity and repair. Brain Res Brain Res Review 36, 175–84.

    Article  CAS  Google Scholar 

  • Kondo T, Raff M (2000) Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science 289, 1754–7.

    Article  PubMed  CAS  Google Scholar 

  • Kosaka T, Hama K (1986) Three-dimensional structure of astrocytes in the rat dentate gyrus. J Comp Neurol 249, 242–60.

    Article  PubMed  CAS  Google Scholar 

  • Kuhn HG, Dickinson-Anson H, Gage FH (1996) Neurogenesis in the dentate gyrus of the adult rat: Age-related decrease of neuronal progenitor proliferation. J Neurosci 16, 2027–33.

    PubMed  CAS  Google Scholar 

  • Leavitt BR, Hernit-Grant CS, Macklis JD (1999) Mature astrocytes transform into transitional radial glia within adult mouse neocortex that supports directed migration of transplanted immature neurons. Exp Neurol 157, 43–57.

    Article  PubMed  CAS  Google Scholar 

  • Lim DA, Alvarez-Buylla A (1999) Interaction between astrocytes and adult subventricular zone precursors stimulates neurogenesis. Proc Natl Acad Sci USA 96, 7526–31.

    Article  PubMed  CAS  Google Scholar 

  • Lim DA, Tramontin AD, Trevejo JM, Herrera DG, Garcia-Verdugo JM, Alvarez-Buylla A (2000) Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28, 713–26.

    Article  PubMed  CAS  Google Scholar 

  • Lois C, Alvarez-Buylla A (1993) Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. Proc Natl Acad Sci USA 90, 2074–7.

    Article  PubMed  CAS  Google Scholar 

  • Lois C, Alvarez-Buylla A (1994) Long-distance neuronal migration in the adult mammalian brain. Science 264, 1145–8.

    Article  PubMed  CAS  Google Scholar 

  • Louissaint Jr A, Rao S, Leventhal C, Goldman SA (2002) Coordinated interaction of neurogenesis and angiogcnesis in the adult songbird brain. Neuron 34, 945–60.

    Article  PubMed  CAS  Google Scholar 

  • Luskin MB (1993) Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 11, 173–89.

    Article  PubMed  CAS  Google Scholar 

  • Mercier F, Kisato JT, Hatton GI (2001) Connexin 26 and basic fibroblast growth factor arc expressed primarily in the subpial and subependymal layers in adult brain parenchyma: Roles in stem cell proliferation and morphological plasticity? J Comp Neurol 431, 88–104.

    Article  PubMed  CAS  Google Scholar 

  • Mercier FJTK, Hatton GI (2002) Anatomy of the brain neurogenic zones revisited: Fractones and the fibroblast/macrophage network. J Comp Neurol 451, 170–88.

    Article  PubMed  Google Scholar 

  • Miyata T, Kawaguchi A, Okano H, Ogawa M (2001) Asymmetric inheritance of radial glial fibers by cortical neurons. Neuron 31, 727–41.

    Article  PubMed  CAS  Google Scholar 

  • Mugnaini E (1986) Cell junctions of astrocytes, ependyma, and related cells in the mammalian central nervous system, with emphasis on the hypothesis of a generalized functional synsytium of supporting cells. In: Astrocytes: Development, Morphology, and Regional Specialization of Astrocytes (Fedoroff, SVA, ed.). Academic Press, New York, 329–71.

    Google Scholar 

  • Noctor SC, Flint AC, Weissman TA, Darnmerman RS, Kriegstein AR (2001) Neurons derived from radial glial cells establish radial units in neocortex. Nature 409, 714–20.

    Article  PubMed  CAS  Google Scholar 

  • Ono K, Tomasiewicz H, Magnuson T, Rutishauser U (1994) NCAM mutation inhibits tangential neuronal migration and is phenocopied by enzymatic removal of polysialic acid. Neuron 13, 595–609.

    Article  PubMed  CAS  Google Scholar 

  • Palmer TD, Markakis EA, Willhoite AR, Safar F, Gage FH (1999) Fibroblast growth factor-2 activates a latent neurogenic program in neural stem cells from diverse regions of the adult CNS. J Neurosci 19, 8487–97.

    PubMed  CAS  Google Scholar 

  • Palmer TD, Willhoite AR, Gage FH (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425, 479–94.

    Article  PubMed  CAS  Google Scholar 

  • Parent JM, Yu TW, Leibowitz RT, Geschwind DR, Sloviter RS, Lowenstein DR (1997) Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci 17, 3727–38.

    PubMed  CAS  Google Scholar 

  • Raisman G (1985) Specialized neuroglial arrangement may explain the capacity of vomeronasal axons to reinnervate central neurons. Neuroscience 14, 237–54.

    Article  PubMed  CAS  Google Scholar 

  • Rakic P (2002) Adult neurogenesis in mammals: An identity crisis. J Neurosci 22, 614–18.

    PubMed  Google Scholar 

  • Ramon y, Cajal S (1995) Histology of the Nervous System of Man and Vertebrates. Oxford University Press, Oxford.

    Google Scholar 

  • Rickmann M, Amaral DG, Cowan WM (1987) Organization of radial glial cells during the development of the rat dentate gyrus. J Comp Neurol 264, 449–79.

    Article  PubMed  CAS  Google Scholar 

  • Rutishauser U, Landmesser L (1996) Polysialic acid in the vertebrate nervous system: A promoter of plasticity in cell-cell interactions. Trends Neurosci 19, 422–7.

    PubMed  CAS  Google Scholar 

  • Schmidt-Kastner R, Szymas J (1990) Immunohistochemistry of glial fibrillary acidic protein, vimentin and S-100 protein for study of astrocytes in hippocampus of rat. J Chem Neuroanat 3, 179–92.

    PubMed  CAS  Google Scholar 

  • Seki T (2002a) Expression patterns of immature neuronal markers (PSA-NCAM, CRMP-4 and NeuroD) in the hippocampus of young adult and aged rodents. J Neurosci Res 70, 327–34.

    Article  PubMed  CAS  Google Scholar 

  • Seki T (2002b) Hippocampal adult neurogenesis occurs in a microenvironment provided by PSA-NCAM-expressing immature neurons. J Neurosci Res 69, 772–83.

    Article  PubMed  CAS  Google Scholar 

  • Seki T, Arai Y (1993a) Distribution and possible roles of the highly polysialylated neural cell adhesion molecule (NCAMH) in the developing and adult central nervous system. Neurosci Res 17, 265–90.

    Article  PubMed  CAS  Google Scholar 

  • Seki T, Arai Y (1993b) Highly polysialylated neural cell adhesion molecule (NCAM-H) is expressed by newly generated granule cells in the dentate gyrus of the adult rat. J Neurosci 13, 2351–8.

    PubMed  CAS  Google Scholar 

  • Seki T, Arai Y (1995) Age-related production of new granule cells in the adult dentate gyrus. Neuroreport 6, 2479–82.

    Article  PubMed  CAS  Google Scholar 

  • Seki T, Arai Y (1999) Temporal and spacial relationships between PSA-NCAM expressing, newly generated granule cells, and radial glia-like cells in the adult dentate gyrus. J Comp Neurol 410, 503–13.

    Article  PubMed  CAS  Google Scholar 

  • Seri B, Garcia-Verdugo JM, McEwen BS, Alvarez-Buylla A (2001) Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci 21, 7153–60.

    PubMed  CAS  Google Scholar 

  • Shihabuddin LS, Homer PJ, Ray J, Gage FH (2000) Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus. J Neurosci 20, 8727–35.

    PubMed  CAS  Google Scholar 

  • Shihabuddin LS, Ray J, Gage FH (1997) FGF-2 is sufficient to isolate progenitors found in the adult mammalian spinal cord. Exp Neurol 148, 577–86.

    Article  PubMed  CAS  Google Scholar 

  • Sievers J, Hartmann D, Peblemarm FW, Berry M (1992) Development of astroglial cells in the proliferative matrices, the granule cell layer, and the hippocampal fissure of the hamster dentate gyrus. J Comp Neurol 320, 1–32.

    Article  PubMed  CAS  Google Scholar 

  • Song H, Stevens CF, Gage FH (2002) Astroglia induce neurogenesis from adult neural stem cells. Nature 417, 39–44.

    Article  PubMed  CAS  Google Scholar 

  • Soriano E, Alvarado-Mallart RM, Dumesnil N, Del Rio JA, Sotelo C (1997) Cajal Retzius cells regulate the radial glia phenotype in the adult and developing cerebellum and alter granule cell migration. Neuron 18, 563–77.

    Article  PubMed  CAS  Google Scholar 

  • Storms SD, Rutishauser U (1998) A role for polysialic acid in neural cell adhesion molecule heterophilic binding to proteoglycans. J Biol Chem 273, 27 124–9.

    Google Scholar 

  • Suhonen JO, Peterson DA, Ray J, Gage FH (1996) Differentiation of adult hippocampus-derived progenitors into olfactory neurons in vivo. Nature 383, 624–7.

    Article  PubMed  CAS  Google Scholar 

  • Tamamaki N, Nakamura K, Okamoto K, Kaneko T (2001) Radial glia is a progenitor of neocortical neurons in the developing cerebral cortex. Neurosci Res 41, 51–60.

    Article  PubMed  CAS  Google Scholar 

  • Valverde F, Santacana M, Heredia M (1992) Formation of an olfactory glomerulus: Morphological aspects of development and organization. Neuroscience 49, 255–75.

    Article  PubMed  CAS  Google Scholar 

  • Vutskits L, Djebbara-Hannas Z, Zhang H et al. (2001) PSA-NCAM modulates BDNF-dependent survival and differentiation of cortical neurons. Eur J Neurosci 13, 1391–402.

    Article  PubMed  CAS  Google Scholar 

  • Wichterle H, Garcia-Verdugo JM, Alvarez-Buylla A (1997) Direct evidence for homotypic, glia-independent neuronal migration. Neuron 18, 779–91.

    Article  PubMed  CAS  Google Scholar 

  • Yayon A, Klagsbrun M, Esko JD, Leder P, Ornitz DM (1991) Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor. Cell 64, 841–8.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Anatomy, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyoku, 113-8421, Tokyo, Japan

    Tatsunori Seki

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Seki, T. Microenvironmental elements supporting adult hippocampal neurogenesis. Anato Sci Int 78, 69–78 (2003). https://doi.org/10.1046/j.0022-7722.2003.00043.x

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