Cell and Tissue Research

, Volume 329, Issue 3, pp 409–420 | Cite as

Immunohistological markers for staging neurogenesis in adult hippocampus

Review

Abstract

Neurogenesis in the adult dentate gyrus (DG) of the hippocampus occurs constitutively throughout postnatal life, and the rate of neurogenesis within the DG can be altered under various physiological and pathophysiological conditions. Adult neurogenesis includes the process in which the division of a precursor cell takes place and the multi-step process (proliferation, differentiation, migration, targeting, and synaptic integration) that ends with the formation of a postmitotic functionally integrated new neuron. During specific time-frames of adult neurogenesis, various markers are expressed that correlate with the differentiation steps along the pathway from early progenitor cells to newly generated postmitotic neurons within the DG. Markers that are currently widely used for the investigation of adult hippocampal neurogenesis are: glial fibrillary acidic protein, nestin, Pax6, NeuroD, PSA-NCAM, doublecortin, TUC-4, Tuj-1, and calretinin. The discovery and development of specific markers that allow the time-course and fate of neurons to be followed during adult neurogenesis in a detailed and precise fashion are not only helpful for gaining further insights into the genesis of new neurons in the hippocampus, but also might be applicable to the development of strategies for therapeutic interventions.

Keywords

Neurogenesis Hippocampus BrdU Progenitor Precursor 

Notes

Acknowledgements

The author wishes to thank Georg Kuhn for his critical and helpful comments.

References

  1. Altman J, Das GD (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124:319–335PubMedCrossRefGoogle Scholar
  2. Altman J, Das GD (1967) Postnatal neurogenesis in the guinea-pig. Nature 214:1098–1101PubMedCrossRefGoogle Scholar
  3. Ambrogini P, Lattanzi D, Ciuffoli S, Agostini D, Bertini L, Stocchi V, Santi S, Cuppini R (2004) Morpho-functional characterization of neuronal cells at different stages of maturation in granule cell layer of adult rat dentate gyrus. Brain Res 1017:21–31PubMedCrossRefGoogle Scholar
  4. Baimbridge KG (1992) Calcium-binding proteins in the dentate gyrus. Epilepsy Res Suppl 7:211–220PubMedGoogle Scholar
  5. Bauer S, Patterson PH (2005) The cell cycle-apoptosis connection revisited in the adult brain. J Cell Biol 171:641–650PubMedCrossRefGoogle Scholar
  6. Bedard A, Gravel C, Parent A (2006) Chemical characterization of newly generated neurons in the striatum of adult primates. Exp Brain Res 170:501–512PubMedCrossRefGoogle Scholar
  7. Belluzzi O, Benedusi M, Ackman J, LoTurco JJ (2003) Electrophysiological differentiation of new neurons in the olfactory bulb. J Neurosci 23:10411–10418PubMedGoogle Scholar
  8. Ben-Hur T, Rogister B, Murray K, Rougon G, Dubois-Dalcq M (1998) Growth and fate of PSA-NCAM+ precursors of the postnatal brain. J Neurosci 18:5777–5788PubMedGoogle Scholar
  9. 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 USA 99:11464–11469PubMedCrossRefGoogle Scholar
  10. Bolton SJ, Perry VH (1998) Differential blood-brain barrier breakdown and leucocyte recruitment following excitotoxic lesions in juvenile and adult rats. Exp Neurol 154:231–240PubMedCrossRefGoogle Scholar
  11. Brandt MD, Jessberger S, Steiner B, Kronenberg G, Reuter K, Bick-Sander A, Behrens W von der, 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
  12. Brook GA, Perez-Bouza A, Noth J, Nacimiento W (1999) Astrocytes re-express nestin in deafferented target territories of the adult rat hippocampus. NeuroReport 10:1007–1011PubMedCrossRefGoogle Scholar
  13. 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
  14. Bull ND, Bartlett PF (2005) The adult mouse hippocampal progenitor is neurogenic but not a stem cell. J Neurosci 25:10815–10821PubMedCrossRefGoogle Scholar
  15. Cameron HA, McKay RD (2001) Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. J Comp Neurol 435:406–417PubMedCrossRefGoogle Scholar
  16. 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 56:337–344PubMedCrossRefGoogle Scholar
  17. Cao F, Hata R, Zhu P, Ma YJ, Tanaka J, Hanakawa Y, Hashimoto K, Niinobe M, Yoshikawa K, Sakanaka M (2006) Overexpression of SOCS3 inhibits astrogliogenesis and promotes maintenance of neural stem cells. J Neurochem 98:459–470PubMedCrossRefGoogle Scholar
  18. Carlen M, Cassidy RM, Brismar H, Smith GA, Enquist LW, Frisen J (2002) Functional integration of adult-born neurons. Curr Biol 12:606–608PubMedCrossRefGoogle Scholar
  19. Cecchini T, Ciaroni S, Ferri P, Ambrogini P, Cuppini R, Santi S, Del Grande P (2003) Alpha-tocopherol, an exogenous factor of adult hippocampal neurogenesis regulation. J Neurosci Res 73:447–455PubMedCrossRefGoogle Scholar
  20. Cooper-Kuhn CM, Kuhn HG (2002) Is it all DNA repair? Methodological considerations for detecting neurogenesis in the adult brain. Brain Res Dev Brain Res 134:13–21PubMedCrossRefGoogle Scholar
  21. Cornford EM, Oldendorf WH (1986) Epilepsy and the blood-brain barrier. Adv Neurol 44:787–812PubMedGoogle Scholar
  22. Couillard-Despres S, Winner B, Schaubeck S, Aigner R, Vroemen M, Weidner N, Bogdahn U, Winkler J, Kuhn HG, Aigner L (2005) Doublecortin expression levels in adult brain reflect neurogenesis. Eur J Neurosci 21:1–14PubMedCrossRefGoogle Scholar
  23. Couillard-Despres S, Winner B, Karl C, Lindemann G, Schmid P, Aigner R, Laemke J, Bogdahn U, Winkler J, Bischofberger J, Aigner L (2006) Targeted transgene expression in neuronal precursors: watching young neurons in the old brain. Eur J Neurosci 24:1535–1545PubMedCrossRefGoogle Scholar
  24. Cremer H, Chazal G, Lledo PM, Rougon G, Montaron MF, Mayo W, Le Moal M, Abrous DN (2000) PSA-NCAM: an important regulator of hippocampal plasticity. Int J Dev Neurosci 18:213–220PubMedCrossRefGoogle Scholar
  25. Dayer AG, Ford AA, Cleaver KM, Yassaee M, Cameron HA (2003) Short-term and long-term survival of new neurons in the rat dentate gyrus. J Comp Neurol 460:563–572PubMedCrossRefGoogle Scholar
  26. Dayer AG, Cleaver KM, Abouantoun T, Cameron HA (2005) New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors. J Cell Biol 168:415–427PubMedCrossRefGoogle Scholar
  27. Dityatev A, Dityateva G, Sytnyk V, Delling M, Toni N, Nikonenko I, Muller D, Schachner M (2004) Polysialylated neural cell adhesion molecule promotes remodeling and formation of hippocampal synapses. J Neurosci 24:9372–9382PubMedCrossRefGoogle Scholar
  28. Doetsch F, Garcia-Verdugo JM, varez-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
  29. Dominguez MI, Blasco-Ibanez JM, Crespo C, Marques-Mari AI, Martinez-Guijarro FJ (2003) Calretinin/PSA-NCAM immunoreactive granule cells after hippocampal damage produced by kainic acid and DEDTC treatment in mouse. Brain Res 966:206–217PubMedCrossRefGoogle Scholar
  30. Doyle KL, Khan M, Cunningham AM (2001) Expression of the intermediate filament protein nestin by sustentacular cells in mature olfactory neuroepithelium. J Comp Neurol 437:186–195PubMedCrossRefGoogle Scholar
  31. Drapeau E, Mayo W, Aurousseau C, Le Moal M, Piazza PV, Abrous DN (2003) Spatial memory performances of aged rats in the water maze predict levels of hippocampal neurogenesis. Proc Natl Acad Sci USA 100:14385–14390PubMedCrossRefGoogle Scholar
  32. Duggal N, Schmidt-Kastner R, Hakim AM (1997) Nestin expression in reactive astrocytes following focal cerebral ischemia in rats. Brain Res 768:1–9PubMedCrossRefGoogle Scholar
  33. Easter SS Jr, Ross LS, Frankfurter A (1993) Initial tract formation in the mouse brain. J Neurosci 13:285–299PubMedGoogle Scholar
  34. Eckenhoff MF, Rakic P (1984) Radial organization of the hippocampal dentate gyrus: a Golgi, ultrastructural, and immunocytochemical analysis in the developing rhesus monkey. J Comp Neurol 223:1–21PubMedCrossRefGoogle Scholar
  35. Eckenhoff MF, Rakic P (1988) Nature and fate of proliferative cells in the hippocampal dentate gyrus during the life span of the rhesus monkey. J Neurosci 8:2729–2747PubMedGoogle Scholar
  36. Englund C, Fink A, Lau C, Pham D, Daza RA, Bulfone A, Kowalczyk T, Hevner RF (2005) Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex. J Neurosci 25:247–251PubMedCrossRefGoogle Scholar
  37. Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH (1998) Neurogenesis in the adult human hippocampus. Nat Med 4:1313–1317PubMedCrossRefGoogle Scholar
  38. Fernandez A, Radmilovich M, Trujillo-Cenoz O (2002) Neurogenesis and gliogenesis in the spinal cord of turtles. J Comp Neurol 453:131–144PubMedCrossRefGoogle Scholar
  39. 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
  40. 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 23:247–256PubMedCrossRefGoogle Scholar
  41. 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
  42. Garcia AD, Doan NB, Imura T, Bush TG, Sofroniew MV (2004) GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain. Nat Neurosci 7:1233–1241PubMedCrossRefGoogle Scholar
  43. Gleeson JG, Lin PT, Flanagan LA, Walsh CA (1999) Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons. Neuron 23:257–271PubMedCrossRefGoogle Scholar
  44. Goldman SA, Nottebohm F (1983) Neuronal production, migration, and differentiation in a vocal control nucleus of the adult female canary brain. Proc Natl Acad Sci USA 80:2390–2394PubMedCrossRefGoogle Scholar
  45. Götz M, Stoykova A, Gruss P (1998) Pax6 controls radial glia differentiation in the cerebral cortex. Neuron 21:1031–1044PubMedCrossRefGoogle Scholar
  46. Gould BB, Rakic P (1981) The total number, time or origin and kinetics of proliferation of neurons comprising the deep cerebellar nuclei in the rhesus monkey. Exp Brain Res 44:195–206PubMedCrossRefGoogle Scholar
  47. Gould E, Reeves AJ, Fallah M, Tanapat P, Gross CG, Fuchs E (1999a) Hippocampal neurogenesis in adult Old World primates. Proc Natl Acad Sci USA 96:5263–5267PubMedCrossRefGoogle Scholar
  48. Gould E, Reeves AJ, Graziano MS, Gross CG (1999b) Neurogenesis in the neocortex of adult primates. Science 286:548–552PubMedCrossRefGoogle Scholar
  49. Gould E, Vail N, Wagers M, Gross CG (2001) Adult-generated hippocampal and neocortical neurons in macaques have a transient existence. Proc Natl Acad Sci USA 98:10910–10917PubMedCrossRefGoogle Scholar
  50. Gulyas AI, Miettinen R, Jacobowitz DM, Freund TF (1992) Calretinin is present in non-pyramidal cells of the rat hippocampus-I. A new type of neuron specifically associated with the mossy fibre system. Neuroscience 48:1–27PubMedCrossRefGoogle Scholar
  51. Hartfuss E, Galli R, Heins N, Gotz M (2001) Characterization of CNS precursor subtypes and radial glia. Dev Biol 229:15–30PubMedCrossRefGoogle Scholar
  52. Heins N, Malatesta P, Cecconi F, Nakafuku M, Tucker KL, Hack MA, Chapouton P, Barde YA, Gotz M (2002) Glial cells generate neurons: the role of the transcription factor Pax6. Nat Neurosci 5:308–315PubMedCrossRefGoogle Scholar
  53. Hevner RF, Hodge RD, Daza RA, Englund C (2006) Transcription factors in glutamatergic neurogenesis: conserved programs in neocortex, cerebellum, and adult hippocampus. Neurosci Res 55:223–233PubMedCrossRefGoogle Scholar
  54. Itoh T, Satou T, Nishida S, Hashimoto S, Ito H (2006) Cultured rat astrocytes give rise to neural stem cells. Neurochem Res 31:1381–1387PubMedCrossRefGoogle Scholar
  55. Jacobowitz DM, Winsky L (1991) Immunocytochemical localization of calretinin in the forebrain of the rat. J Comp Neurol 304:198–218PubMedCrossRefGoogle Scholar
  56. Kalman M, Ajtai BM (2001) A comparison of intermediate filament markers for presumptive astroglia in the developing rat neocortex: immunostaining against nestin reveals more detail, than GFAP or vimentin. Int J Dev Neurosci 19:101–108PubMedCrossRefGoogle Scholar
  57. Kawai T, Takagi N, Miyake-Takagi K, Okuyama N, Mochizuki N, Takeo S (2004) Characterization of BrdU-positive neurons induced by transient global ischemia in adult hippocampus. J Cereb Blood Flow Metab 24:548–555PubMedCrossRefGoogle Scholar
  58. Kempermann G, Kuhn HG, Gage FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386:493–495PubMedCrossRefGoogle Scholar
  59. 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
  60. Kempermann G, Jessberger S, Steiner B, Kronenberg G (2004) Milestones of neuronal development in the adult hippocampus. Trends Neurosci 27:447–452PubMedCrossRefGoogle Scholar
  61. Kim SH, Kim HB, Jang MH, Lim BV, Kim YJ, Kim YP, Kim SS, Kim EH, Kim CJ (2002) Treadmill exercise increases cell proliferation without altering of apoptosis in dentate gyrus of Sprague-Dawley rats. Life Sci 71:1331–1340PubMedCrossRefGoogle Scholar
  62. Koizumi H, Higginbotham H, Poon T, Tanaka T, Brinkman BC, Gleeson JG (2006) Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain. Nat Neurosci 9:779–786PubMedCrossRefGoogle Scholar
  63. Kornack DR, Rakic P (1999) Continuation of neurogenesis in the hippocampus of the adult macaque monkey. Proc Natl Acad Sci USA 96:5768–5773PubMedCrossRefGoogle Scholar
  64. 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
  65. 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 16:2027–2033PubMedGoogle Scholar
  66. Lee JE, Hollenberg SM, Snider L, Turner DL, Lipnick N, Weintraub H (1995) Conversion of Xenopus ectoderm into neurons by NeuroD, a basic helix-loop-helix protein. Science 268:836–844PubMedCrossRefGoogle Scholar
  67. Levitt P, Rakic P (1980) Immunoperoxidase localization of glial fibrillary acidic protein in radial glial cells and astrocytes of the developing rhesus monkey brain. J Comp Neurol 193:815–840PubMedCrossRefGoogle Scholar
  68. Lind D, Franken S, Kappler J, Jankowski J, Schilling K (2005) Characterization of the neuronal marker NeuN as a multiply phosphorylated antigen with discrete subcellular localization. J Neurosci Res 79:295–302PubMedCrossRefGoogle Scholar
  69. Liu J, Solway K, Messing RO, Sharp FR (1998) Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils. J Neurosci 18:7768–7778PubMedGoogle Scholar
  70. Liu M, Pleasure SJ, Collins AE, Noebels JL, Naya FJ, Tsai MJ, Lowenstein DH (2000) Loss of BETA2/NeuroD leads to malformation of the dentate gyrus and epilepsy. Proc Natl Acad Sci USA 97:865–870PubMedCrossRefGoogle Scholar
  71. Liu Y, Fujise N, Kosaka T (1996) Distribution of calretinin immunoreactivity in the mouse dentate gyrus. I. General description. Exp Brain Res 108:389–403PubMedCrossRefGoogle Scholar
  72. Llorens-Martin M, Torres-Aleman I, Trejo JL (2006) Pronounced individual variation in the response to the stimulatory action of exercise on immature hippocampal neurons. Hippocampus 16:480–490PubMedCrossRefGoogle Scholar
  73. Luo C, Xu H, Li XM (2005) Quetiapine reverses the suppression of hippocampal neurogenesis caused by repeated restraint stress. Brain Res 1063:32–39PubMedCrossRefGoogle Scholar
  74. Luskin MB (1993) Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 11:173–189PubMedCrossRefGoogle Scholar
  75. Luskin MB (1994) Neuronal cell lineage in the vertebrate central nervous system. FASEB J 8:722–730PubMedGoogle Scholar
  76. Maekawa M, Takashima N, Arai Y, Nomura T, Inokuchi K, Yuasa S, Osumi N (2005) Pax6 is required for production and maintenance of progenitor cells in postnatal hippocampal neurogenesis. Genes Cells 10:1001–1014PubMedCrossRefGoogle Scholar
  77. Maslov AY, Barone TA, Plunkett RJ, Pruitt SC (2004) Neural stem cell detection, characterization, and age-related changes in the subventricular zone of mice. J Neurosci 24:1726–1733PubMedCrossRefGoogle Scholar
  78. Menezes JR, Luskin MB (1994) Expression of neuron-specific tubulin defines a novel population in the proliferative layers of the developing telencephalon. J Neurosci 14:5399–5416PubMedGoogle Scholar
  79. Merrill DA, Karim R, Darraq M, Chiba AA, Tuszynski MH (2003) Hippocampal cell genesis does not correlate with spatial learning ability in aged rats. J Comp Neurol 459:201–207PubMedCrossRefGoogle Scholar
  80. Miettinen R, Gulyas AI, Baimbridge KG, Jacobowitz DM, Freund TF (1992) Calretinin is present in non-pyramidal cells of the rat hippocampus. II. Co-existence with other calcium binding proteins and GABA. Neuroscience 48:29–43PubMedCrossRefGoogle Scholar
  81. Miller MW, Nowakowski RS (1988) Use of bromodeoxyuridine-immunohistochemistry to examine the proliferation, migration and time of origin of cells in the central nervous system. Brain Res 457:44–52PubMedCrossRefGoogle Scholar
  82. Ming GL, Song H (2005) Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci 28:223–250PubMedCrossRefGoogle Scholar
  83. Minturn JE, Fryer HJ, Geschwind DH, Hockfield S (1995a) TOAD-64, a gene expressed early in neuronal differentiation in the rat, is related to unc-33, a C. elegans gene involved in axon outgrowth. J Neurosci 15:6757–6766PubMedGoogle Scholar
  84. Minturn JE, Geschwind DH, Fryer HJ, Hockfield S (1995b) Early postmitotic neurons transiently express TOAD-64, a neural specific protein. J Comp Neurol 355:369–379PubMedCrossRefGoogle Scholar
  85. Mitra R, Sundlass K, Parker KJ, Schatzberg AF, Lyons DM (2006) Social stress-related behavior affects hippocampal cell proliferation in mice. Physiol Behav 89:123–127PubMedCrossRefGoogle Scholar
  86. Miyata T, Maeda T, Lee JE (1999) NeuroD is required for differentiation of the granule cells in the cerebellum and hippocampus. Genes Dev 13:1647–1652PubMedGoogle Scholar
  87. Mullen RJ, Buck CR, Smith AM (1992) NeuN, a neuronal specific nuclear protein in vertebrates. Development 116:201–211PubMedGoogle Scholar
  88. Munoz-Elias G, Woodbury D, Black IB (2003) Marrow stromal cells, mitosis, and neuronal differentiation: stem cell and precursor functions. Stem Cells 21:437–448PubMedCrossRefGoogle Scholar
  89. Nacher J, Blasco-Ibanez JM, McEwen BS (2002) Non-granule PSA-NCAM immunoreactive neurons in the rat hippocampus. Brain Res 930:1–11PubMedCrossRefGoogle Scholar
  90. Nacher J, Varea E, Blasco-Ibanez JM, Castillo-Gomez E, Crespo C, Martinez-Guijarro FJ, McEwen BS (2005) Expression of the transcription factor Pax 6 in the adult rat dentate gyrus. J Neurosci Res 81:753–761PubMedCrossRefGoogle Scholar
  91. Namba T, Mochizuki H, Onodera M, Mizuno Y, Namiki H, Seki T (2005) The fate of neural progenitor cells expressing astrocytic and radial glial markers in the postnatal rat dentate gyrus. Eur J Neurosci 22:1928–1941PubMedCrossRefGoogle Scholar
  92. Ngwenya LB, Peters A, Rosene DL (2006) Maturational sequence of newly generated neurons in the dentate gyrus of the young adult rhesus monkey. J Comp Neurol 498:204–216PubMedCrossRefGoogle Scholar
  93. Nilsson M, Perfilieva E, Johansson U, Orwar O, Eriksson PS (1999) Enriched environment increases neurogenesis in the adult rat dentate gyrus and improves spatial memory. J Neurobiol 39:569–578PubMedCrossRefGoogle Scholar
  94. Nottebohm F (1985) Neuronal replacement in adulthood. Ann N Y Acad Sci 457:143–161PubMedCrossRefGoogle Scholar
  95. Nowakowski RS, Hayes NL (2000) New neurons: extraordinary evidence or extraordinary conclusion? Science 288:771PubMedCrossRefGoogle Scholar
  96. Pardridge WM, Connor JD, Crawford IL (1975) Permeability changes in the blood-brain barrier: causes and consequences. CRC Crit Rev Toxicol 3:159–199PubMedGoogle Scholar
  97. 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 17:3727–3738PubMedGoogle Scholar
  98. Paton JA, Nottebohm FN (1984) Neurons generated in the adult brain are recruited into functional circuits. Science 225:1046–1048PubMedCrossRefGoogle Scholar
  99. Pham K, Nacher J, Hof PR, McEwen BS (2003) Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus. Eur J Neurosci 17:879–886PubMedCrossRefGoogle Scholar
  100. Praag H van, Christie BR, Sejnowski TJ, Gage FH (1999) Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci USA 96:13427–13431PubMedCrossRefGoogle Scholar
  101. Praag H van, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH (2002) Functional neurogenesis in the adult hippocampus. Nature 415:1030–1034PubMedCrossRefGoogle Scholar
  102. Quinn CC, Gray GE, Hockfield S (1999) A family of proteins implicated in axon guidance and outgrowth. J Neurobiol 41:158–164PubMedCrossRefGoogle Scholar
  103. Ra SM, Kim H, Jang MH, Shin MC, Lee TH, Lim BV, Kim CJ, Kim EH, Kim KM, Kim SS (2002) Treadmill running and swimming increase cell proliferation in the hippocampal dentate gyrus of rats. Neurosci Lett 333:123–126PubMedCrossRefGoogle Scholar
  104. Rami A, Brehier A, Thomasset M, Rabie A (1987) Cholecalcin (28-kDa calcium-binding protein) in the rat hippocampus: development in normal animals and in altered thyroid states. An immunocytochemical study. Dev Biol 124:228–238PubMedCrossRefGoogle Scholar
  105. 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
  106. Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–1710PubMedCrossRefGoogle Scholar
  107. Rolls ET (2000) Memory systems in the brain. Annu Rev Psychol 51:599–630PubMedCrossRefGoogle Scholar
  108. Sahin KS, Mahmood A, Li Y, Yavuz E, Chopp M (1999) Expression of nestin after traumatic brain injury in rat brain. Brain Res 840:153–157CrossRefGoogle Scholar
  109. Sandi C, Merino JJ, Cordero MI, Touyarot K, Venero C (2001) Effects of chronic stress on contextual fear conditioning and the hippocampal expression of the neural cell adhesion molecule, its polysialylation, and L1. Neuroscience 102:329–339PubMedCrossRefGoogle Scholar
  110. Sasaki T, Kitagawa K, Yagita Y, Sugiura S, Omura-Matsuoka E, Tanaka S, Matsushita K, Okano H, Tsujimoto Y, Hori M (2006) Bcl2 enhances survival of newborn neurons in the normal and ischemic hippocampus. J Neurosci Res 84:1187–1196PubMedCrossRefGoogle Scholar
  111. Scharfman H, Goodman J, Macleod A, Phani S, Antonelli C, Croll S (2005) Increased neurogenesis and the ectopic granule cells after intrahippocampal BDNF infusion in adult rats. Exp Neurol 192:348–356PubMedCrossRefGoogle Scholar
  112. Schmidt-Kastner R, Humpel C (2002) Nestin expression persists in astrocytes of organotypic slice cultures from rat cortex. Int J Dev Neurosci 20:29–38PubMedCrossRefGoogle Scholar
  113. Scott BW, Wang S, Burnham WM, De Boni U, Wojtowicz JM (1998) Kindling-induced neurogenesis in the dentate gyrus of the rat. Neurosci Lett 248:73–76PubMedCrossRefGoogle Scholar
  114. 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 70:327–334PubMedCrossRefGoogle Scholar
  115. Seki T (2002b) Hippocampal adult neurogenesis occurs in a microenvironment provided by PSA-NCAM-expressing immature neurons. J Neurosci Res 69:772–783PubMedCrossRefGoogle Scholar
  116. Seki T, Arai Y (1991) The persistent expression of a highly polysialylated NCAM in the dentate gyrus of the adult rat. Neurosci Res 12:503–513PubMedCrossRefGoogle Scholar
  117. 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 410:503–513PubMedCrossRefGoogle Scholar
  118. Sequier JM, Hunziker W, Richards G (1988) Localization of calbindin D28 mRNA in rat tissues by in situ hybridization. Neurosci Lett 86:155–160PubMedCrossRefGoogle Scholar
  119. Seress L, Gulyas AI, Freund TF (1991) Parvalbumin- and calbindin D28k-immunoreactive neurons in the hippocampal formation of the macaque monkey. J Comp Neurol 313:162–177PubMedCrossRefGoogle Scholar
  120. Seress L, Gulyas AI, Freund TF (1992) Pyramidal neurons are immunoreactive for calbindin D28k in the CA1 subfield of the human hippocampus. Neurosci Lett 138:257–260PubMedCrossRefGoogle Scholar
  121. Seri B, Garcia-Verdugo JM, McEwen BS, varez-Buylla A (2001) Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci 21:7153–7160PubMedGoogle Scholar
  122. Seri B, Garcia-Verdugo JM, Collado-Morente L, McEwen BS, varez-Buylla A (2004) Cell types, lineage, and architecture of the germinal zone in the adult dentate gyrus. J Comp Neurol 478:359–378PubMedCrossRefGoogle Scholar
  123. Seri B, Herrera DG, Gritti A, Ferron S, Collado L, Vescovi A, Garcia-Verdugo JM, varez-Buylla A (2006) Composition and organization of the SCZ: a large germinal layer containing neural stem cells in the adult mammalian brain. Cereb Cortex 16 (Suppl 1):i103–i111PubMedCrossRefGoogle Scholar
  124. Shors TJ, Townsend DA, Zhao M, Kozorovitskiy Y, Gould E (2002) Neurogenesis may relate to some but not all types of hippocampal-dependent learning. Hippocampus 12:578–584PubMedCrossRefGoogle Scholar
  125. 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
  126. Steiner B, Klempin F, Wang L, Kott M, Kettenmann H, Kempermann G (2006) Type-2 cells as link between glial and neuronal lineage in adult hippocampal neurogenesis. Glia 54:805–814PubMedCrossRefGoogle Scholar
  127. Sun W, Winseck A, Vinsant S, Park OH, Kim H, Oppenheim RW (2004) Programmed cell death of adult-generated hippocampal neurons is mediated by the proapoptotic gene Bax. J Neurosci 24:11205–11213PubMedCrossRefGoogle Scholar
  128. Takemura NU (2005) Evidence for neurogenesis within the white matter beneath the temporal neocortex of the adult rat brain. Neuroscience 134:121–132PubMedCrossRefGoogle Scholar
  129. Tamimi R, Steingrimsson E, Copeland NG, Dyer-Montgomery K, Lee JE, Hernandez R, Jenkins NA, Tapscott SJ (1996) The NEUROD gene maps to human chromosome 2q32 and mouse chromosome 2. Genomics 34:418–421PubMedCrossRefGoogle Scholar
  130. Uda M, Ishido M, Kami K, Masuhara M (2006) Effects of chronic treadmill running on neurogenesis in the dentate gyrus of the hippocampus of adult rat. Brain Res 1104:64–72PubMedCrossRefGoogle Scholar
  131. Van der Borght K, Wallinga AE, Luiten PG, Eggen BJ, Zee EA van der (2005) Morris water maze learning in two rat strains increases the expression of the polysialylated form of the neural cell adhesion molecule in the dentate gyrus but has no effect on hippocampal neurogenesis. Behav Neurosci 119:926–932PubMedCrossRefGoogle Scholar
  132. Van Kampen JM, Hagg T, Robertson HA (2004) Induction of neurogenesis in the adult rat subventricular zone and neostriatum following dopamine D receptor stimulation. Eur J Neurosci 19:2377–2387PubMedCrossRefGoogle Scholar
  133. Venero C, Herrero AI, Touyarot K, Cambon K, Lopez-Fernandez MA, Berezin V, Bock E, Sandi C (2006) Hippocampal up-regulation of NCAM expression and polysialylation plays a key role on spatial memory. Eur J Neurosci 23:1585–1595PubMedCrossRefGoogle Scholar
  134. Warner-Schmidt JL, Duman RS (2006) Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus 16:239–249PubMedCrossRefGoogle Scholar
  135. Winner B, Cooper-Kuhn CM, Aigner R, Winkler J, Kuhn HG (2002) Long-term survival and cell death of newly generated neurons in the adult rat olfactory bulb. Eur J Neurosci 16:1681–1689PubMedCrossRefGoogle Scholar
  136. Wolf HK, Buslei R, Schmidt-Kastner R, Schmidt-Kastner PK, Pietsch T, Wiestler OD, Blümcke I (1996) NeuN: a useful neuronal marker for diagnostic histopathology. J Histochem Cytochem 44:1167–1171PubMedGoogle Scholar
  137. 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
  138. 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 76:282–295PubMedCrossRefGoogle Scholar
  139. Yoo YM, Lee U, Kim YJ (2005) Apoptosis and nestin expression in the cortex and cultured astrocytes following 6-OHDA administration. Neurosci Lett 382:88–92PubMedCrossRefGoogle Scholar
  140. Yoshimi K, Ren YR, Seki T, Yamada M, Ooizumi H, Onodera M, Saito Y, Murayama S, Okano H, Mizuno Y, Mochizuki H (2005) Possibility for neurogenesis in substantia nigra of Parkinsonian brain. Ann Neurol 58:31–40PubMedCrossRefGoogle Scholar
  141. Young D, Lawlor PA, Leone P, Dragunow M, During MJ (1999) Environmental enrichment inhibits spontaneous apoptosis, prevents seizures and is neuroprotective. Nat Med 5:448–453PubMedCrossRefGoogle Scholar
  142. Yue F, Chen B, Wu D, Dong K, Zeng SE, Zhang Y (2006) Biological properties of neural progenitor cells isolated from the hippocampus of adult cynomolgus monkeys. Chin Med J (Engl) 119:110–116Google Scholar
  143. 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 USA 100:7925–7930PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Interdisciplinary Center for Neurosciences (IZN), Department of NeuroanatomyUniversity of HeidelbergHeidelbergGermany

Personalised recommendations