Abstract
It is of great interest to identify new neurons in the adult human brain, but the persistence of neurogenesis in the subventricular zone (SVZ) and the existence of the rostral migratory stream (RMS)-like pathway in the adult human forebrain remain highly controversial. In the present study, we have described the general configuration of the RMS in adult monkey, fetal human and adult human brains. We provide evidence that neuroblasts exist continuously in the anterior ventral SVZ and RMS of the adult human brain. The neuroblasts appear singly or in pairs without forming chains; they exhibit migratory morphologies and co-express the immature neuronal markers doublecortin, polysialylated neural cell adhesion molecule and βIII-tubulin. Few of these neuroblasts appear to be actively proliferating in the anterior ventral SVZ but none in the RMS, indicating that neuroblasts distributed along the RMS are most likely derived from the ventral SVZ. Interestingly, no neuroblasts are found in the adult human olfactory bulb. Taken together, our data suggest that the SVZ maintains the ability to produce neuroblasts in the adult human brain.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Ming GL, Song H . Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci 2005; 28:223–250.
Kriegstein A, Alvarez-Buylla A . The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci 2009; 32:149–184.
Suh H, Deng W, Gage FH . Signaling in adult neurogenesis. Annu Rev Cell Dev Biol 2009; 25:253–275.
Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A . Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 1999; 97:703–716.
Mirzadeh Z, Merkle FT, Soriano-Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A . Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell Stem Cell 2008; 3:265–278.
Lois C, Garcia-Verdugo JM, Alvarez-Buylla A . Chain migration of neuronal precursors. Science 1996; 271:978–981.
Doetsch F, Alvarez-Buylla A . Network of tangential pathways for neuronal migration in adult mammalian brain. Proc Natl Acad Sci USA 1996; 93:14895–14900.
Luskin MB . Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 1993; 11:173–189.
Gil-Perotin S, Duran-Moreno M, Belzunegui S, Luquin MR, Garcia-Verdugo JM . Ultrastructure of the subventricular zone in Macaca fascicularis and evidence of a mouse-like migratory stream. J Comp Neurol 2009; 514:533–554.
Pencea V, Bingaman KD, Freedman LJ, Luskin MB . Neurogenesis in the subventricular zone and rostral migratory stream of the neonatal and adult primate forebrain. Exp Neurol 2001; 172:1–16.
Kornack DR, Rakic P . The generation, migration, and differentiation of olfactory neurons in the adult primate brain. Proc Natl Acad Sci USA 2001; 98:4752–4757.
Bedard A, Levesque M, Bernier PJ, Parent A . 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 2002; 16:1917–1924.
Sawamoto K, Hirota Y, Alfaro-Cervello C, et al. Cellular composition and organization of the subventricular zone and rostral migratory stream in the adult and neonatal common marmoset brain. J Comp Neurol 2011; 519:690–713.
Sanai N, Tramontin AD, Quinones-Hinojosa A, et al. Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 2004; 427:740–744.
Leonard BW, Mastroeni D, Grover A, et al. Subventricular zone neural progenitors from rapid brain autopsies of elderly subjects with and without neurodegenerative disease. J Comp Neurol 2009; 515:269–294.
van den Berge SA, Middeldorp J, Zhang CE, et al. Longterm quiescent cells in the aged human subventricular neurogenic system specifically express GFAP-delta. Aging Cell 2010; 9:313–326.
Eriksson PS, Perfilieva E, Bjork-Eriksson T, et al. Neurogenesis in the adult human hippocampus. Nat Med 1998; 4:1313–1317.
Weickert CS, Webster MJ, Colvin SM, et al. Localization of epidermal growth factor receptors and putative neuroblasts in human subependymal zone. J Comp Neurol 2000; 423:359–372.
Guerrero-Cazares H, Gonzalez-Perez O, Soriano-Navarro M, et al. Cytoarchitecture of the lateral ganglionic eminence and rostral extension of the lateral ventricle in the human fetal brain. J Comp Neurol 2011; 519:1165–1180.
Sanai N, Berger MS, Garcia-Verdugo JM, Alvarez-Buylla A . Comment on “Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension”. Science 2007; 318:393.
Curtis MA, Kam M, Nannmark U, et al. Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 2007; 315:1243–1249.
Kam M, Curtis MA, McGlashan SR, et al. The cellular composition and morphological organization of the rostral migratory stream in the adult human brain. J Chem Neuroanat 2009; 37:196–205.
Quinones-Hinojosa A, Sanai N, Soriano-Navarro M, et al. Cellular composition and cytoarchitecture of the adult human subventricular zone: a niche of neural stem cells. J Comp Neurol 2006; 494:415–434.
Liu YW, Curtis MA, Gibbons HM, et al. Doublecortin expression in the normal and epileptic adult human brain. Eur J Neurosci 2008; 28:2254–2265.
Humphrey TJ . The development of the olfactory and the accessory olfactory formations in human embryos and fetuses. J Comp Neurol 1940; 73:431–468.
Gleeson JG, Lin PT, Flanagan LA, Walsh CA . Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons. Neuron 1999; 23:257–271.
Verwer RW, Sluiter AA, Balesar RA, et al. Mature astrocytes in the adult human neocortex express the early neuronal marker doublecortin. Brain 2007; 130:3321–3335.
Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A . Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci 1997; 17:5046–5061.
Zhang XM, Cai Y, Chu Y, et al. Doublecortin-expressing cells persist in the associative cerebral cortex and amygdala in aged nonhuman primates. Front Neuroanat 2009; 3:17.
Gomez-Climent MA, Castillo-Gomez E, Varea E, et al. A population of prenatally generated cells in the rat paleocortex maintains an immature neuronal phenotype into adulthood. Cereb Cortex 2008; 18:2229–2240.
Menezes JR, Smith CM, Nelson KC, Luskin MB . The division of neuronal progenitor cells during migration in the neonatal mammalian forebrain. Mol Cell Neurosci 1995; 6:496–508.
Mullen RJ, Buck CR, Smith AM . NeuN, a neuronal specific nuclear protein in vertebrates. Development 1992; 116:201–211.
Bedard A, Parent A . Evidence of newly generated neurons in the human olfactory bulb. Brain Res 2004; 151:159–168.
Kaneko N, Marin O, Koike M, et al. New neurons clear the path of astrocytic processes for their rapid migration in the adult brain. Neuron 2010; 67:213–223.
Mai JK, Paxinos G, Voss T . Atlas of the Human Brain. 3rd Edition. San Diego: Academic Press, 2008.
Acknowledgements
This work was supported by the National Natural Science Foundation of China (30870804, 30900425, 30970949, 30990261, 30821002 and 31028009), Shanghai Shu-Guang project (09SG05) and National Basic Research Program of China (2010CB945500, 2011CB504400). We thank the staff at Chinese Brain Bank Center, Wuhan, China and Red Cross Society of China, Shanghai Branch at the Fudan University for providing access to donated human brains. We thank Dr John Rubinstein (University of California, San Francisco, USA) for his helpful comments on the manuscript.
Author information
Authors and Affiliations
Corresponding author
Additional information
(Supplementary information is linked to the online version of the paper on the Cell Research website.)
Supplementary information
Supplementary information, Figure S1
Neuroblasts in the adult monkey SVZ, olfactory tract and OB. (PDF 185 kb)
Supplementary information, Figure S2
The antibodies used in the present study recognize specific human antigens. (PDF 827 kb)
Supplementary information, Figure S3
Dcx+ cells exist in the ventral SVZ and RMS of the adult human brain. (PDF 156 kb)
Supplementary information, Figure S4
Dcx+ cells exist in the rostral limb of the RMS of the adult human brain. (PDF 335 kb)
Supplementary information, Figure S5
Most PSA-NCAM+ and Tuj1+ cells do not express Dcx in the adult human olfactory tract and OB. (PDF 173 kb)
Rights and permissions
About this article
Cite this article
Wang, C., Liu, F., Liu, YY. et al. Identification and characterization of neuroblasts in the subventricular zone and rostral migratory stream of the adult human brain. Cell Res 21, 1534–1550 (2011). https://doi.org/10.1038/cr.2011.83
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/cr.2011.83
Keywords
This article is cited by
-
Restoration of Adult Neurogenesis by Intranasal Administration of Gangliosides GD3 and GM1 in The Olfactory Bulb of A53T Alpha-Synuclein-Expressing Parkinson’s-Disease Model Mice
Molecular Neurobiology (2023)
-
Adult Neural Stem Cell Migration Is Impaired in a Mouse Model of Alzheimer’s Disease
Molecular Neurobiology (2022)
-
Adult human neurogenesis: early studies clarify recent controversies and go further
Metabolic Brain Disease (2022)
-
Developmental Origins of Human Cortical Oligodendrocytes and Astrocytes
Neuroscience Bulletin (2022)
-
Characterization of substantia nigra neurogenesis in homeostasis and dopaminergic degeneration: beneficial effects of the microneurotrophin BNN-20
Stem Cell Research & Therapy (2021)