Neurogenesis in Monkey and Human Adult Brain

  • Andréanne Bédard
  • Patrick J. Bernier
  • André Parent


This paper summarizes the results of our studies on adult neurogenesis in some key structures of the monkey and human brain. These results stem from multiple immunocytochemical investigations undertaken with antigens raised against various molecular markers of neurogenesis, either alone or in combination with the DNA synthesis indicator bromodeoxyuridine (BrdU). This approach has allowed us to provide the first detailed picture of the organization of the rostral migratory stream (RMS) in adult squirrel monkeys. Furthermore, studies on human postmortem tissue have revealed, for the first time, that the adult human olfactory bulb is the recipient of neuroblasts that migrate along the RMS and progressively develop a GABAergic or dopaminergic phenotype. A new migratory stream that provides newborn neurons to the amygdala and adjacent piriform cortex has also been visualized in squirrel monkeys. Finally, the striatum of normal adult squirrel monkeys was found to harbor newly generated cells that eventually become projection neurons. The recruitment of such striatal neurons was markedly increased in the presence of brain-derived neurotrophic factor (BDNF), a finding that raises hope for the development of novel therapeutic approaches for the treatment of ­certain neurodegenerative diseases.


Olfactory Bulb Dentate Gyrus Squirrel Monkey Adult Neurogenesis Temporal Stream 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Anterior commissure


Adenoviral vector overexpressing BDNF




Brain-derived neurotrophic factor




Caudal (posterior)




Corpus callosum


Caudate nucleus


Choline acetyltransferase








Dopamine- and cAMP-regulated phosphoprotein of 32 kDa




External plexiform layer


Fiber layer


Glutamic acid decarboxylase


GAD 65 and 67 isoforms


Granular cell layer


Glial fibrillary acidic protein


Glomerular layer




Horizontal limb


Internal capsule


Cell cycle-associated protein


Lateral ventricle


Microtubule-associated protein 2


Mitral cell layer


Nucleus accumbens


Neuronal nuclear protein


Neuronal determination and differentiation transcription factor


Olfactory bulb


Olfactory nerve layer


Olfactory tubercle


Proliferating cell nuclear antigen


Piriform cortex


Posterior limb


Polysialylated neural cell adhesion






Rostral (anterior)


Rostral migratory stream




Subventricular zone


Anterior part of SVZ


Tyrosine hydroxylase


Temporal horn of LV


Temporal migratory stream


Collapsin response mediator protein-4




Vertical limb



This study was supported by grant MT-8756 of the Canadian Institutes for Health Research (CIHR) to A. Parent. A. Bédard and P.J. Bernier were recipients of CIHR Studentships.


  1. Altman J, Das GD (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124:319–336.PubMedCrossRefGoogle Scholar
  2. Arvidsson A, Collin T, Kirik D et al (2002) Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 8:963–970.PubMedCrossRefGoogle Scholar
  3. Bédard A, Parent A (2004) Evidence of newly generated neurons in the human olfactory bulb. Dev Brain Res 151:159–168.CrossRefGoogle Scholar
  4. Bédard A, Cossette M, Lévesque M et al (2002a) Proliferating cells can differentiate into neurons in the striatum of normal adult monkey. Neurosci Lett 328:213–216.PubMedCrossRefGoogle Scholar
  5. Bédard A, Lévesque M, Bernier PJ et al (2002b) The rostral migratory stream in adult squirrel monkeys: contribution of new neurons to the olfactory tubercle and involvement of the antiapoptotic protein Bcl-2. Eur J Neurosci 16:1917–1924.PubMedCrossRefGoogle Scholar
  6. Bédard A, Gravel C, Parent A (2006) Chemical characterization of newly generated neurons in the striatum of adult primates. Exp Brain Res 170:501–512.PubMedCrossRefGoogle Scholar
  7. Bernier PJ, Parent A (1998a) Bcl-2 protein as a marker of neuronal immaturity in postnatal primate brain. J Neurosci 18:2486–2497.PubMedGoogle Scholar
  8. Bernier PJ, Parent A (1998b) The anti-apoptosis bcl-2 proto-oncogene is preferentially expressed in limbic structures of the primate brain. Neuroscience 82:635–640.PubMedCrossRefGoogle Scholar
  9. Bernier PJ, Vinet J, Cossette M et al (2000) Characterization of the subventricular zone in the adult human brain: evidence for Bcl-2 involvement. Neurosci Res 37:67–78.PubMedCrossRefGoogle Scholar
  10. Bernier PJ, Bédard A, Vinet J et al (2002) Newly generated neurons in the amygdala and adjoining cortex of adult primates. Proc Natl Acad Sci USA 99:11464–11469.PubMedCrossRefGoogle Scholar
  11. Cameron HA, Dayer AG (2008) New interneurons in the adult neocortex: small, sparse, but ­significant? Biol Psychiatry 63:650–655.PubMedCrossRefGoogle Scholar
  12. Cameron HA, Woolley CS, McEwen BS et al (1993) Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience 56:337–344.PubMedCrossRefGoogle Scholar
  13. Chmielnicki E, Benraiss A, Economides AN et al (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: 2133–2142.PubMedCrossRefGoogle Scholar
  14. Craig CG, Tropepe V, Morshead CM et al (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
  15. Curtis MA, Kam M, Nannmark U et al (2007) Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 315:1243–1249.PubMedCrossRefGoogle Scholar
  16. Doestch F, Alvarez-Buylla A (1996) Network of tangential pathways for neuronal migration in adult mammalian brain. Proc Natl Acad Sci USA 93:14895–14900.CrossRefGoogle Scholar
  17. Eriksson PS, Perfilieva E, Björk-Eriksson T et al (1998) Neurogenesis in the adult human hippocampus, Nat Med 4:1313–1317.PubMedCrossRefGoogle Scholar
  18. Feess-Higgins A, Larroche JC (1987) Development of the human foetal brain, an anatomical atlas. Masson, Paris.Google Scholar
  19. Gould E (2007) How widespread is adult neurogenesis in mammals? Nat Rev Neurosci 8:481–488.PubMedCrossRefGoogle Scholar
  20. Gould E, Tanapat P, McEwen BS et al (1998) Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc Natl Acad Sci USA 95:3168–3171.PubMedCrossRefGoogle Scholar
  21. Gould E, Reeves AJ, Fallah M et al (1999a) Hippocampal neurogenesis in adult Old World primates. Proc Natl Acad Sci USA 96:5263–5267.PubMedCrossRefGoogle Scholar
  22. Gould E, Reeves AJ, Graziano MS et al (1999b) Neurogenesis in the neocortex of adult primates. Science 286:548–552.PubMedCrossRefGoogle Scholar
  23. Gould E, Vail N, Wagers M et al (2001) Adult-generated hippocampal and neocortical neurons in macaques have a transient existence. Proc Natl Acad Sci USA 98:10910–10917.PubMedCrossRefGoogle Scholar
  24. Gravel C, Gotz R, Lorrain A et al (1997) Adenoviral gene transfer of ciliary neurotrophic factor and brain-derived neurotrophic factor leads to long-term survival of axotomized motor neurons. Nat Med 3:765–770.PubMedCrossRefGoogle Scholar
  25. Kaplan MS, Hinds JW (1977) Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. Science 197:1092–1094.PubMedCrossRefGoogle Scholar
  26. Kempermann G, Kuhn HG, Gage FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386:493–495.PubMedCrossRefGoogle Scholar
  27. Kornack DR, Rakic P (1999) Continuation of neurogenesis in the hippocampus of the adult macaque monkey. Proc Natl Acad Sci USA 96:5768–5773.PubMedCrossRefGoogle Scholar
  28. Kornack DR, Rakic P (2001) The generation, migration, and differentiation of olfactory neurons in the adult primate brain. Proc Natl Acad Sci USA 98:4752–4757.PubMedCrossRefGoogle Scholar
  29. 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 16:2027–2033.PubMedGoogle Scholar
  30. Luskin MB (1993) Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 11:173–189.PubMedCrossRefGoogle Scholar
  31. Mizuno K, Carnahan J, Nawa H (1994) Brain-derived neurotrophic factor promotes differentiation of striatal GABAergic neurons. Dev Biol 165:243–256.PubMedCrossRefGoogle Scholar
  32. Pencea V, Bingaman KD, Freedman LJ et al (2001a) Neurogenesis in the subventricular zone and rostral migratory stream of the neonatal and adult primate forebrain. Exp Neurol 172:1–16.PubMedCrossRefGoogle Scholar
  33. Pencea V, Bingaman KD, Wiegand SJ et al (2001b) Infusion of brain-derived neurotrophic factor into 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
  34. Reynolds BA, Tetzlaff W, Weiss S (1992) A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. J Neurosci 12:4565–4574.PubMedGoogle Scholar
  35. Saghatelyan A, Roux P, Migliore M et al (2005) Activity-dependent adjustments of the inhibitory network in the olfactory bulb following early postnatal deprivation. Neuron 46:103–116PubMedCrossRefGoogle Scholar
  36. Sanai N, Berger MS, Garcia-Verdugo JM et al (2007) Comment on “Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension”. Science 318:393.PubMedCrossRefGoogle Scholar
  37. Seki T (2002) Hippocampal adult neurogenesis occurs in a microenvironment provided by PSA-NCAM-expressing immature neurons. J Neurosci Res 69:772–783.PubMedCrossRefGoogle Scholar
  38. Steiner B, Wolf S, Kempermann G (2006) Adult neurogenesis and neurodegenerative disease. Regen Med 1:15–28.PubMedCrossRefGoogle Scholar
  39. Ventimiglia R, Mather PE, Jones BE et al (1995) The neurotrophins BDNF, NT-3 and NT-4/5 promote survival and morphological and biochemical differentiation of striatal neurons in vitro. Eur J Neurosci 7:213–222.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  • Andréanne Bédard
    • 1
  • Patrick J. Bernier
    • 1
  • André Parent
    • 1
  1. 1.Centre de Recherche Université Laval Robert-GiffardBeauportCanada

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