Brain Structure and Function

, Volume 212, Issue 1, pp 19–35 | Cite as

Local origin and activity-dependent generation of nestin-expressing protoplasmic astrocytes in CA1

  • Golo Kronenberg
  • Li-Ping Wang
  • Martine Geraerts
  • Harish Babu
  • Michael Synowitz
  • Paloma Vicens
  • Gudrun Lutsch
  • Rainer Glass
  • Masahiro Yamaguchi
  • Veerle Baekelandt
  • Zeger Debyser
  • Helmut Kettenmann
  • Gerd Kempermann
Original Article

Abstract

Since reports that precursor cells in the adult subventricular zone (SVZ) contribute to regenerative neuro- and gliogenesis in CA1, we wondered whether a similar route of migration might also exist under physiological conditions. Permanent labeling of SVZ precursor cells with a lentiviral vector for green fluorescent protein did not reveal any migration from the SVZ into CA1 in the intact murine brain. However, in a nestin-GFP reporter mouse we found proliferating cells within the corpus callosum/alveus region expressing nestin and glial fibrillary acidic protein similar to precursor cells in the neighboring neurogenic region of the adult dentate gyrus. Within 3 weeks of BrdU administration, BrdU-positive nestin-GFP-expressing protoplasmic astrocytes emerged in CA1. Similar to precursor cells isolated from the dentate gyrus and the SVZ, nestin-GFP-expressing cells from corpus callosum/alveus were self-renewing and multipotent in vitro, whereas cells isolated from CA1 were not. Nestin-GFP-expressing cells in CA1 differentiated into postmitotic astrocytes characterized by S100β expression. No new neurons were found in CA1. The number of nestin-GFP-expressing astrocytes in CA1 was increased by environmental enrichment. We conclude that astrogenesis in CA1 is influenced by environmental conditions. However, SVZ precursor cells do not contribute to physiological cellular plasticity in CA1.

Keywords

Nestin Neurogenesis Alveus Migration Gliogenesis Stem cell 

References

  1. 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 137:433–457PubMedCrossRefGoogle Scholar
  2. Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O (2002) Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 8:963–970PubMedCrossRefGoogle Scholar
  3. Baekelandt V, Eggermont K, Michiels M, Nuttin B, Debyser Z (2003) Optimized lentiviral vector production and purification procedure prevents immune response after transduction of mouse brain. Gene Ther 10:1933–1940PubMedCrossRefGoogle Scholar
  4. Bergles DE, Roberts JD, Somogyi P, Jahr CE (2000) Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus. Nature 405:187–191PubMedCrossRefGoogle Scholar
  5. Brandt MD, Jessberger S, Steiner B, Kronenberg G, Reuter K, Bick-Sander A, Von der Behrens W, Kempermann G (2003) Transient calretinin-expression defines early postmitotic step of neuronal differentiation in adult hippocampal neurogenesis of mice. Mol Cell Neurosci 24:603–613PubMedCrossRefGoogle Scholar
  6. Brown JP, Couillard-Despres S, Cooper-Kuhn CM, Winkler J, Aigner L, Kuhn HG (2003) Transient expression of doublecortin during adult neurogenesis. J Comp Neurol 467:1–10PubMedCrossRefGoogle Scholar
  7. Buffo A, Vosko MR, Erturk D, Hamann GF, Jucker M, Rowitch D, Gotz M (2005) Expression pattern of the transcription factor Olig2 in response to brain injuries: implications for neuronal repair. Proc Natl Acad Sci USA 102:18183–18188PubMedCrossRefGoogle Scholar
  8. Bushong EA, Martone ME, Jones YZ, Ellisman MH (2002) Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J Neurosci 22:183–192PubMedGoogle Scholar
  9. Chmielnicki E, Benraiss A, Economides AN, Goldman SA (2004) Adenovirally expressed noggin and brain-derived neurotrophic factor cooperate to induce new medium spiny neurons from resident progenitor cells in the adult striatal ventricular zone. J Neurosci 24:2133–2142PubMedCrossRefGoogle Scholar
  10. D’Ambrosio R, Wenzel J, Schwartzkroin PA, McKhann GM 2nd, Janigro D (1998) Functional specialization and topographic segregation of hippocampal astrocytes. J Neurosci 18:4425–4438PubMedGoogle Scholar
  11. Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A (1997) Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci 17:5046–5061PubMedGoogle Scholar
  12. 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 97:703–716PubMedCrossRefGoogle Scholar
  13. Doetsch F, Petreanu L, Caille I, Garcia-Verdugo JM, Alvarez-Buylla A (2002) EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells. Neuron 36:1021–1034PubMedCrossRefGoogle Scholar
  14. 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 23:373–382PubMedCrossRefGoogle Scholar
  15. Fukuda S, Kato F, Tozuka Y, Yamaguchi M, Miyamoto Y, Hisatsune T (2003) Two distinct subpopulations of nestin-positive cells in adult mouse dentate gyrus. J Neurosci 23:9357–9366PubMedGoogle Scholar
  16. Geraerts M, Michiels M, Baekelandt V, Debyser Z, Gijsbers R (2005) Upscaling of lentiviral vector production by tangential flow filtration. J Gene Med 7:1299–1310PubMedCrossRefGoogle Scholar
  17. Geraerts M, Eggermont K, Hernandez-Acosta P, Garcia-Verdugo JM, Baekelandt V, Debyser Z (2006) Lentiviral vectors mediate efficient and stable gene transfer in adult neural stem cells in vivo. Hum Gene Ther 17:635–650PubMedCrossRefGoogle Scholar
  18. Hacker GW, Graf AH, Thurner J (1990) [Application of silver acetate autometallography in histopathology: a new detection method for use in immunogold silver staining, lectin histochemistry and in situ hybridization]. Verh Dtsch Ges Pathol 74:368–372PubMedGoogle Scholar
  19. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 391:85–100PubMedCrossRefGoogle Scholar
  20. Huang YH, Sinha SR, Tanaka K, Rothstein JD, Bergles DE (2004) Astrocyte glutamate transporters regulate metabotropic glutamate receptor-mediated excitation of hippocampal interneurons. J Neurosci 24:4551–4559PubMedCrossRefGoogle Scholar
  21. Kempermann G, Kuhn HG, Gage FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386:493–495PubMedCrossRefGoogle Scholar
  22. Kempermann G, Gast D, Gage FH (2002) Neuroplasticity in old age: sustained fivefold induction of hippocampal neurogenesis by long-term environmental enrichment. Ann Neurol 52:135–143PubMedCrossRefGoogle Scholar
  23. Kempermann G, Gast D, Kronenberg G, Yamaguchi M, Gage FH (2003) Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice. Development 130:391–399PubMedCrossRefGoogle Scholar
  24. Kokaia Z, Lindvall O (2003) Neurogenesis after ischaemic brain insults. Curr Opin Neurobiol 13:127–132PubMedCrossRefGoogle Scholar
  25. 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 467:455–463PubMedCrossRefGoogle Scholar
  26. Kronenberg G, Wang LP, Synowitz M, Gertz K, Katchanov J, Glass R, Harms C, Kempermann G, Kettenmann H, Endres M (2005) Nestin-expressing cells divide and adopt a complex electrophysiologic phenotype after transient brain ischemia. J Cereb Blood Flow Metab 25(12):1613–1624PubMedCrossRefGoogle Scholar
  27. Laywell ED, Rakic P, Kukekov VG, Holland EC, Steindler DA (2000) Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain. Proc Natl Acad Sci USA 97:13883–13888PubMedCrossRefGoogle Scholar
  28. Lendahl U, Zimmerman LB, McKay RDG (1990) CNS Stem cells express a new class of intermediate filament protein. Cell 60:585–595PubMedCrossRefGoogle Scholar
  29. Levison SW, Goldman JE (1993) Both oligodendrocytes and astrocytes develop from progenitors in the subventricular zone of postnatal rat forebrain. Neuron 10:201–212PubMedCrossRefGoogle Scholar
  30. 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 90:2074–2077PubMedCrossRefGoogle Scholar
  31. Luskin MB (1993) Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 11:173–189PubMedCrossRefGoogle Scholar
  32. Luskin MB, Zigova T, Soteres BJ, Stewart RR (1997) Neuronal progenitor cells derived from the anterior subventricular zone of the neonatal rat forebrain continue to proliferate in vitro and express a neuronal phenotype. Mol Cell Neurosci 8:351–366PubMedCrossRefGoogle Scholar
  33. Magavi S, Leavitt B, Macklis J (2000) Induction of neurogenesis in the neocortex of adult mice. Nature 405:951–955PubMedCrossRefGoogle Scholar
  34. Malatesta P, Hartfuss E, Gotz M (2000) Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage. Development 127:5253–5263PubMedGoogle Scholar
  35. Mignone JL, Kukekov V, Chiang AS, Steindler D, Enikolopov G (2004) Neural stem and progenitor cells in nestin-GFP transgenic mice. J Comp Neurol 469:311–324PubMedCrossRefGoogle Scholar
  36. Nacher J, Crespo C, McEwen BS (2001) Doublecortin expression in the adult rat telencephalon. Eur J Neurosci 14:629–644PubMedCrossRefGoogle Scholar
  37. Nacher J, Alonso-Llosa G, Rosell DR, McEwen BS (2003) NMDA receptor antagonist treatment increases the production of new neurons in the aged rat hippocampus. Neurobiol Aging 24:273–284PubMedCrossRefGoogle Scholar
  38. 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 110:429–441PubMedCrossRefGoogle Scholar
  39. Nishiyama H, Knopfel T, Endo S, Itohara S (2002) Glial protein S100B modulates long-term neuronal synaptic plasticity. Proc Natl Acad Sci USA 99:4037–4042PubMedCrossRefGoogle Scholar
  40. Palmer TD, Ray J, Gage FH (1995) FGF-2-responsive neuronal progenitors reside in proliferative and quiescent regions of the adult rodent brain. Mol Cell Neurosci 6:474–486PubMedCrossRefGoogle Scholar
  41. 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 divers regions of the adult CNS. J Neurosci 19:8487–8497PubMedGoogle Scholar
  42. Parent JM, von dem Bussche N, Lowenstein DH (2006) Prolonged seizures recruit caudal subventricular zone glial progenitors into the injured hippocampus. Hippocampus 16:321–328PubMedCrossRefGoogle Scholar
  43. 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 21:6706–6717PubMedGoogle Scholar
  44. Rao MS, Shetty AK (2004) Efficacy of doublecortin as a marker to analyse the absolute number and dendritic growth of newly generated neurons in the adult dentate gyrus. Eur J Neurosci 19:234–246PubMedCrossRefGoogle Scholar
  45. Rietze R, Poulin P, Weiss S (2000) Mitotically active cells that generate neurons and astrocytes are present in multiple regions of the adult mouse hippocampus. J Comp Neurol 424:397–408PubMedCrossRefGoogle Scholar
  46. Rosenzweig MR (2003) Effects of differential experience on the brain and behavior. Dev Neuropsychol 24:523–540PubMedCrossRefGoogle Scholar
  47. Rosenzweig MR, Bennett EL (1996) Psychobiology of plasticity: effects of training and experience on brain and behavior. Behav Brain Res 78:57–65PubMedCrossRefGoogle Scholar
  48. Savchenko VL, McKanna JA, Nikonenko IR, Skibo GG (2000) Microglia and astrocytes in the adult rat brain: comparative immunocytochemical analysis demonstrates the efficacy of lipocortin 1 immunoreactivity. Neuroscience 96:195–203PubMedCrossRefGoogle Scholar
  49. Seri B, Garcia-Verdugo JM, McEwen BS, Alvarez-Buylla A (2001) Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci 21:7153–7160PubMedGoogle Scholar
  50. Seri B, Garcia-Verdugo JM, Collado-Morente L, McEwen BS, Alvarez-Buylla A (2004) Cell types, lineage, and architecture of the germinal zone in the adult dentate gyrus. J Comp Neurol 478:359PubMedCrossRefGoogle Scholar
  51. Spacek J, Harris KM (1998) Three-dimensional organization of cell adhesion junctions at synapses and dendritic spines in area CA1 of the rat hippocampus. J Comp Neurol 393:58–68PubMedCrossRefGoogle Scholar
  52. Steiner B, Kronenberg G, Jessberger S, Brandt MD, Reuter K, Kempermann G (2004) Differential regulation of gliogenesis in the context of adult hippocampal neurogenesis in mice. Glia 46:41–52PubMedCrossRefGoogle Scholar
  53. Steiner B, Klempin F, Wang LP, Kettenmann H, Kempermann G (2006) Type-2 cells as link between glial and neuronal lineage in adult hippocampal neurogenesis. Glia: PMID: 16958090Google Scholar
  54. Steinhauser C, Kressin K, Kuprijanova E, Weber M, Seifert G (1994) Properties of voltage-activated Na+ and K+ currents in mouse hippocampal glial cells in situ and after acute isolation from tissue slices. Pflugers Arch 428:610–620PubMedCrossRefGoogle Scholar
  55. Sundholm-Peters NL, Yang HK, Goings GE, Walker AS, Szele FG (2005) Subventricular zone neuroblasts emigrate toward cortical lesions. J Neuropathol Exp Neurol 64(12):1089–1100PubMedGoogle Scholar
  56. Tsien JZ, Huerta PT, Tonegawa S (1996) The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory. Cell 87:1327–1338PubMedCrossRefGoogle Scholar
  57. Van Maele B, De Rijck J, De Clercq E, Debyser Z (2003) Impact of the central polypurine tract on the kinetics of human immunodeficiency virus type 1 vector transduction. J Virol 77:4685–4694PubMedCrossRefGoogle Scholar
  58. Van Praag H, Kempermann G, Gage FH (1999) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2:266–270PubMedCrossRefGoogle Scholar
  59. van Praag H, Kempermann G, Gage FH (2000) Neural consequences of environmental enrichment. Nat Rev Neurosci 1:191–198PubMedCrossRefGoogle Scholar
  60. Wang DD, Krueger DD, Bordey A (2003) Biophysical properties and ionic signature of neuronal progenitors of the postnatal subventricular zone in situ. J Neurophysiol 90:2291–2302PubMedCrossRefGoogle Scholar
  61. Williams RW, Rakic P (1988) Three-dimensional counting: an accurate and direct method to estimate numbers of cells in sectioned material. J Comp Neurol 278:344–352PubMedCrossRefGoogle Scholar
  62. Yamaguchi M, Saito H, Suzuki M, Mori K (2000) Visualization of neurogenesis in the central nervous system using nestin promoter-GFP transgenic mice. Neuroreport 11:1991–1996PubMedCrossRefGoogle Scholar
  63. Yamashita T, Ninomiya M, Hernandez Acosta P, Garcia-Verdugo JM, Sunabori T, Sakaguchi M, Adachi K, Kojima T, Hirota Y, Kawase T, Araki N, Abe K, Okano H, Sawamoto K (2006) Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum. J Neurosci 26:6627–6636PubMedCrossRefGoogle Scholar
  64. Yang HK, Sundholm-Peters NL, Goings GE, Walker AS, Hyland K, Szele FG (2004) Distribution of doublecortin expressing cells near the lateral ventricles in the adult mouse brain. J Neurosci Res 76(3):282–295PubMedCrossRefGoogle Scholar
  65. Zufferey R, Dull T, Mandel RJ, Bukovsky A, Quiroz D, Naldini L, Trono D (1998) Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J Virol 72:9873–9880PubMedGoogle Scholar
  66. Zufferey R, Donello JE, Trono D, Hope TJ (1999) Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors. J Virol 73:2886–2892PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Golo Kronenberg
    • 1
    • 2
  • Li-Ping Wang
    • 1
  • Martine Geraerts
    • 3
  • Harish Babu
    • 1
  • Michael Synowitz
    • 1
    • 4
  • Paloma Vicens
    • 1
    • 5
  • Gudrun Lutsch
    • 1
  • Rainer Glass
    • 1
  • Masahiro Yamaguchi
    • 6
  • Veerle Baekelandt
    • 3
  • Zeger Debyser
    • 3
  • Helmut Kettenmann
    • 1
  • Gerd Kempermann
    • 1
    • 7
  1. 1.Max Delbrück Center for Molecular Medicine (MDC), Berlin-BuchBerlinGermany
  2. 2.Department of PsychiatryCharité University MedicineBerlinGermany
  3. 3.Division of Molecular Medicine, Department of Molecular and Cellular MedicineKatholieke Universiteit LeuvenLeuvenBelgium
  4. 4.Department of NeurosurgeryHELIOS Hospital Berlin-BuchBerlinGermany
  5. 5.Department of PsychologyRovira & Virgili UniversityTarragonaSpain
  6. 6.Department of Physiology, Graduate School of MedicineUniversity of TokyoTokyoJapan
  7. 7.Volkswagenstiftung Research Group, Department of Experimental NeurologyCharité University Medicine BerlinBerlinGermany

Personalised recommendations