In the adult brain, neural stem cells have been found in two major niches: the hippocampus and the olfactory bulb. Neurons derived from these stem cells contribute to learning, memory, and the autonomous repair of the brain under pathological conditions. Hence, the physiology of adult neural stem cells has become a significant component of research on synaptic plasticity and neuronal disorders. In addition, the recently developed induced pluripotent stem cell technique provides a powerful tool for researchers engaged in the pathological and pharmacological study of neuronal disorders. In this review, we briefly summarize the research progress in neural stem cells in the adult brain and in the neuropathological application of the induced pluripotent stem cell technique.
Aarsland, D., Londos, E., and Ballard, C. (2009). Parkinson’s disease dementia and dementia with Lewy bodies: different aspects of one entity. Int Psychogeriatr 21, 216-219 . doi: 10.1017/S1041610208008612
2
Ahn, S., and Joyner, A.L. (2005). In vivo analysis of quiescent adult neural stem cells responding to Sonic hedgehog. Nature 437, 894-897 . doi: 10.1038/nature03994
3
Akbarian, S. (2003). The neurobiology of Rett syndrome. Neurobscientist 9, 57-63 . doi: 10.1177/1073858402239591
4
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, 433-457 . doi: 10.1002/cne.901370404
5
Altman, J., and Das, G.D. (1965). Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124, 319-335 . doi: 10.1002/cne.901240303
6
Arvidsson, A., Collin, T., Kirik, D., Kokaia, Z., and Lindvall, O. (2002). Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 8, 963-970 . doi: 10.1038/nm747
7
Balordi, F., and Fishell, G. (2007). Hedgehog signaling in the subventricular zone is required for both the maintenance of stem cells and the migration of newborn neurons. J Neurosci 27, 5936-5947 . doi: 10.1523/JNEUROSCI.1040-07.2007
8
Bonaguidi, M.A., McGuire, T., Hu, M., Kan, L., Samanta, J., and Kessler, J.A. (2005). LIF and BMP signaling generate separate and discrete types of GFAP-expressing cells. Development 132, 5503-5514 . doi: 10.1242/dev.02166
9
Bonfanti, L., Aimar, P., Ponti, G., and Canalia, N. (2008). Immuno- electromicroscopic approach for the study of neural stem cell niches. Vet Res Commun 32, S107-S109 . doi: 10.1007/s11259-008-9103-5
10
Bonfanti, L., and Peretto, P. (2007). Radial glial origin of the adult neural stem cells in the subventricular zone. Prog Neurobiol 83, 24-36 . doi: 10.1016/j.pneurobio.2006.11.002
11
Bonfanti, L., and Theodosis, D.T. (2009). Polysialic acid and activity-dependent synapse remodeling. Cell Adh Migr 3, 43-50 . doi: 10.4161/cam.3.1.7258
12
Braak, H., Sastre, M., and Del Tredici, K. (2007). Development of alpha-synuclein immunoreactive astrocytes in the forebrain parallels stages of intraneuronal pathology in sporadic Parkinson’s disease. Acta Neuropathol 114, 231-241 . doi: 10.1007/s00401-007-0244-3
13
Brennand, K.J., Simone, A., Jou, J., Gelboin-Burkhart, C., Tran, N., Sangar, S., Li, Y., Mu, Y., Chen, G., Yu, D., . (2011). Modelling schizophrenia using human induced pluripotent stem cells. Nature 473, 221-225 . doi: 10.1038/nature09915
14
Brill, M.S., Snapyan, M., Wohlfrom, H., Ninkovic, J., Jawerka, M., Mastick, G.S., Ashery-Padan, R., Saghatelyan, A., Berninger, B., and G?tz, M. (2008). A dlx2- and pax6-dependent transcriptional code for periglomerular neuron specification in the adult olfactory bulb. J Neurosci 28, 6439-6452 . doi: 10.1523/JNEUROSCI.0700-08.2008
15
Bürglen, L., Lefebvre, S., Clermont, O., Burlet, P., Viollet, L., Cruaud, C., Munnich, A., and Melki, J. (1996). Structure and organization of the human survival motor neurone (SMN) gene. Genomics 32, 479-482 . doi: 10.1006/geno.1996.0147
16
Cameron, H.A., McEwen, B.S., and Gould, E. (1995). Regulation of adult neurogenesis by excitatory input and NMDA receptor activation in the dentate gyrus. J Neurosci 15, 4687-4692 .
17
Cameron, H.A., and McKay, R.D. (2001). Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. J Comp Neurol 435, 406-417 . doi: 10.1002/cne.1040
18
Cao, L., Jiao, X., Zuzga, D.S., Liu, Y., Fong, D.M., Young, D., and During, M.J. (2004). VEGF links hippocampal activity with neurogenesis, learning and memory. Nat Genet 36, 827-835 . doi: 10.1038/ng1395
19
Carpenter, W.T. Jr, and Buchanan, R.W. (1994). Schizophrenia. N Engl J Med 330, 681-690 . doi: 10.1056/NEJM199403103301006
20
Chahrour, M., and Zoghbi, H.Y. (2007). The story of Rett syndrome: from clinic to neurobiology. Neuron 56, 422-437 . doi: 10.1016/j.neuron.2007.10.001
21
Chambers, S.M., Fasano, C.A., Papapetrou, E.P., Tomishima, M., Sadelain, M., and Studer, L. (2009). Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 27, 275-280 . doi: 10.1038/nbt.1529
22
Chen, Q., Nakajima, A., Choi, S.H., Xiong, X., Sisodia, S.S., and Tang, Y.P. (2008). Adult neurogenesis is functionally associated with AD-like neurodegeneration. Neurobiol Dis 29, 316-326 . doi: 10.1016/j.nbd.2007.09.005
23
Cherubini, E., Griguoli, M., Safiulina, V., and Lagostena, L. (2011). The depolarizing action of GABA controls early network activity in the developing hippocampus. Mol Neurobiol 43, 97-106 . doi: 10.1007/s12035-010-8147-z
24
Chiang, C.H., Su, Y., Wen, Z., Yoritomo, N., Ross, C.A., Margolis, R.L., Song, H., and Ming, G.L. (2011). Integration-free induced pluripotent stem cells derived from schizophrenia patients with a DISC1 mutation. Mol Psychiatry 16, 358-360 . doi: 10.1038/mp.2011.13
25
Choi, S.H., Veeraraghavalu, K.,Lazarov, O., Marler, S., Ransohoff, R.M., Ramirez, J.M., and Sisodia, S.S. (2008). Non-cell-autonomous effects of presenilin 1 variants on enrichment-mediated hippocampal progenitor cell proliferation and differentiation. Neuron 59, 568-580 . doi: 10.1016/j.neuron.2008.07.033
26
Corotto, F.S., Henegar, J.A., and Maruniak, J.A. (1993). Neurog-enesis persists in the subependymal layer of the adult mouse brain. Neurosci Lett 149, 111-114 . doi: 10.1016/0304-3940(93)90748-A
27
Crews, L., Mizuno, H., Desplats, P., Rockenstein, E., Adame, A., Patrick, C., Winner, B., Winkler, J., and Masliah, E. (2008). Alpha-synuclein alters Notch-1 expression and neurogenesis in mouse embryonic stem cells and in the hippocampus of transgenic mice. J Neurosci 28, 4250-4260 . doi: 10.1523/JNEUROSCI.0066-08.2008
28
Curtis, M.A., Kam, M., and Faull, R.L. (2011). Neurogenesis in humans. Eur J Neurosci 33, 1170-1174 . doi: 10.1111/j.1460-9568.2011.07616.x
29
Deisseroth, K., Singla, S., Toda, H., Monje, M., Palmer, T.D., and Malenka, R.C. (2004). Excitation-neurogenesis coupling in adult neural stem/progenitor cells. Neuron 42, 535-552 . doi: 10.1016/S0896-6273(04)00266-1
30
Demars, M., Hu, Y.S., Gadadhar, A., and Lazarov, O. (2010). Impaired neurogenesis is an early event in the etiology of familial Alzheimer’s disease in transgenic mice. J Neurosci Res 88, 2103-2117 . doi: 10.1002/jnr.22387
31
Dimos, J.T., Rodolfa, K.T., Niakan, K.K., Weisenthal, L.M., Mitsumoto, H., Chung, W., Croft, G.F., Saphier, G., Leibel, R., Goland, R., . (2008). Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321, 1218-1221 . doi: 10.1126/science.1158799
32
Doetsch, F., García-Verdugo, J.M., and Alvarez-Buylla, A. (1997). Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci 17, 5046-5061 .
33
Donovan, M.H., Yazdani, U., Norris, R.D., Games, D., German, D.C., and Eisch, A.J. (2006). Decreased adult hippocampal neurogenesis in the PDAPP mouse model of Alzheimer’s disease. J Comp Neurol 495, 70-83 . doi: 10.1002/cne.20840
Ehm, O., G?ritz, C., Covic, M., Sch?ffner, I., Schwarz, T.J., Karaca, E., Kempkes, B., Kremmer, E., Pfrieger, F.W., Espinosa, L., . (2010). RBPJkappa-dependent signaling is essential for long-term maintenance of neural stem cells in the adult hippocampus. J Neurosci 30, 13794-13807 . doi: 10.1523/JNEUROSCI.1567-10.2010
36
Englund, C., Fink, A., Lau, C., Pham, D., Daza, R.A., Bulfone, A., Kowalczyk, T., and Hevner, R.F. (2005). Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex. J Neurosci 25, 247-251 . doi: 10.1523/JNEUROSCI.2899-04.2005
37
Favaro, R., Valotta, M., Ferri, A.L., Latorre, E., Mariani, J., Giachino, C., Lancini, C., Tosetti, V., Ottolenghi, S., Taylor, V., . (2009). Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. Nat Neurosci 12, 1248-1256 . doi: 10.1038/nn.2397
38
Ferri, A.L., Cavallaro, M., Braida, D., Di Cristofano, A., Canta, A., Vezzani, A., Ottolenghi, S., Pandolfi, P.P., Sala, M., DeBiasi, S., . (2004). Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain. Development 131, 3805-3819 . doi: 10.1242/dev.01204
39
Fournier, N.M., and Duman, R.S. (2012). Role of vascular endothelial growth factor in adult hippocampal neurogenesis: Implications for the pathophysiology and treatment of depression. Behav Brain Res 227, 440-449 . doi: 10.1016/j.bbr.2011.04.022
40
Gadadhar, A., Marr, R., and Lazarov, O. (2011). Presenilin-1 regulates neural progenitor cell differentiation in the adult brain. J Neurosci 31, 2615-2623 . doi: 10.1523/JNEUROSCI.4767-10.2011
41
Ge, S., Goh, E.L., Sailor, K.A., Kitabatake, Y., Ming, G.L., and Song, H. (2006). GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature 439, 589-593 . doi: 10.1038/nature04404
42
Goedert, M. (2001). Alpha-synuclein and neurodegenerative diseases. Nat Rev Neurosci 2, 492-501 . doi: 10.1038/35081564
43
Han, Y.G., Spassky, N., Romaguera-Ros, M., Garcia-Verdugo, J.M., Aguilar, A., Schneider-Maunoury, S., and Alvarez-Buylla, A. (2008). Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells. Nat Neurosci 11, 277-284 . doi: 10.1038/nn2059
44
Hardy, J., and Selkoe, D.J. (2002). The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297, 353-356 . doi: 10.1126/science.1072994
45
Haughey, N.J., Nath, A., Chan, S.L., Borchard, A.C., Rao, M.S., and Mattson, M.P. (2002). Disruption of neurogenesis by amyloid beta-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer’s disease. J Neurochem 83, 1509-1524 . doi: 10.1046/j.1471-4159.2002.01267.x
46
Herold, S., Jagasia, R., Merz, K., Wassmer, K., and Lie, D.C. (2011). CREB signalling regulates early survival, neuronal gene expression and morphological development in adult subventr-icular zone neurogenesis. Mol Cell Neurosci 46, 79-88 . doi: 10.1016/j.mcn.2010.08.008
47
Hevner, R.F., Shi, L., Justice, N., Hsueh, Y., Sheng, M., Smiga, S., Bulfone, A., Goffinet, A.M., Campagnoni, A.T., and Rubenstein, J.L. (2001). Tbr1 regulates differentiation of the preplate and layer 6. Neuron 29, 353-366 . doi: 10.1016/S0896-6273(01)00211-2
48
Hodge, R.D., and Hevner, R.F. (2011). Expression and actions of transcription factors in adult hippocampal neurogenesis. Dev Neurobiol 71, 680-689 . doi: 10.1002/dneu.20882
49
Hodge, R.D.,Kowalczyk, T.D., Wolf, S.A., Encinas, J.M., Rippey, C., Enikolopov, G., Kempermann, G., and Hevner, R.F. (2008). Intermediate progenitors in adult hippocampal neurogenesis: Tbr2 expression and coordinate regulation of neuronal output. J Neurosci 28, 3707-3717 . doi: 10.1523/JNEUROSCI.4280-07.2008
50
Hotta, A., Cheung, A.Y., Farra, N., Vijayaragavan, K., Séguin, C.A., Draper, J.S., Pasceri, P., Maksakova, I.A., Mager, D.L., Rossant, J., . (2009). Isolation of human iPS cells using EOS lentiviral vectors to select for pluripotency. Nat Methods 6, 370-376 . doi: 10.1038/nmeth.1325
51
Hu, M., Sun, Y.J., Zhou, Q.G., Chen, L., Hu, Y., Luo, C.X., Wu, J.Y., Xu, J.S., Li, L.X., and Zhu, D.Y. (2008). Negative regulation of neurogenesis and spatial memory by NR2B-containing NMDA receptors. J Neurochem 106, 1900-1913 . doi: 10.1111/j.1471-4159.2008.05554.x
52
Imayoshi, I., Sakamoto, M., Yamaguchi, M., Mori, K., and Kageyama, R. (2010). Essential roles of Notch signaling in maintenance of neural stem cells in developing and adult brains. J Neurosci 30, 3489-3498 . doi: 10.1523/JNEUROSCI.4987-09.2010
Jin, K., Galvan, V., Xie, L., Mao, X.O., Gorostiza, O.F., Bredesen, D.E., and Greenberg, D.A. (2004). Enhanced neurogenesis in Alzheimer’s disease transgenic (PDGF-APPSw,Ind) mice. Proc Natl Acad Sci U S A 101, 13363-13367 . doi: 10.1073/pnas.0403678101
56
Jin, K., Sun, Y., Xie, L., Batteur, S., Mao, X.O., Smelick, C., Logvinova, A., and Greenberg, D.A. (2003). Neurogenesis and aging: FGF-2 and HB-EGF restore neurogenesis in hippocampus and subventricular zone of aged mice. Aging Cell 2, 175-183 . doi: 10.1046/j.1474-9728.2003.00046.x
57
Jin, K., Zhu, Y., Sun, Y., Mao, X.O., Xie, L., and Greenberg, D.A. (2002). Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci U S A 99, 11946-11950 . doi: 10.1073/pnas.182296499
58
Jones, K.S., and Connor, B. (2011). Proneural transcription factors Dlx2 and Pax6 are altered in adult SVZ neural precursor cells following striatal cell loss. Mol Cell Neurosci 47, 53-60 . doi: 10.1016/j.mcn.2011.03.001
59
Kang, E., Burdick, K.E., Kim, J.Y., Duan, X., Guo, J.U., Sailor, K.A., Jung, D.E., Ganesan, S., Choi, S., Pradhan, D., . (2011). Interaction between FEZ1 and DISC1 in regulation of neuronal development and risk for schizophrenia. Neuron 72, 559-571 . doi: 10.1016/j.neuron.2011.09.032
60
Kawasaki, H., Mizuseki, K., Nishikawa, S., Kaneko, S., Kuwana, Y., Nakanishi, S., Nishikawa, S.I., and Sasai, Y. (2000). Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron 28, 31-40 . doi: 10.1016/S0896-6273(00)00083-0
61
Kitayama, T., Yoneyama, M., Tamaki, K., and Yoneda, Y. (2004). Regulation of neuronal differentiation by N-methyl-D-aspartate receptors expressed in neural progenitor cells isolated from adult mouse hippocampus. J Neurosci Res 76, 599-612 . doi: 10.1002/jnr.20095
62
Kohwi, M., Osumi, N., Rubenstein, J.L., and Alvarez-Buylla, A. (2005). Pax6 is required for making specific subpopulations of granule and periglomerular neurons in the olfactory bulb. J Neurosci 25, 6997-7003 . doi: 10.1523/JNEUROSCI.1435-05.2005
63
Komitova, M., and Eriksson, P.S. (2004). Sox-2 is expressed by neural progenitors and astroglia in the adult rat brain. Neurosci Lett 369, 24-27 . doi: 10.1016/j.neulet.2004.07.035
64
Kuhn, H.G., Dickinson-Anson, H., and Gage, F.H. (1996). Neuro-genesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16, 2027-2033 .
65
Lee, G.,Papapetrou, E.P., Kim, H., Chambers, S.M., Tomishima, M.J., Fasano, C.A., Ganat, Y.M., Menon, J., Shimizu, F., Viale, A., . (2009). Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature 461, 402-406 . doi: 10.1038/nature08320
66
Lee, K.W., Woon, P.S., Teo, Y.Y., and Sim, K. (2012). Genome wide association studies (GWAS) and copy number variation (CNV) studies of the major psychoses: what have we learnt? Neurosci Biobehav Rev 36, 556-571 . doi: 10.1016/j.neubiorev.2011.09.001
67
Licht, T., Goshen, I., Avital, A., Kreisel, T., Zubedat, S., Eavri, R., Segal, M., Yirmiya, R., and Keshet, E. (2011). Reversible modulations of neuronal plasticity by VEGF. Proc Natl Acad Sci U S A 108, 5081-5086 . doi: 10.1073/pnas.1007640108
Lie, D.C., Dziewczapolski, G., Willhoite, A.R., Kaspar, B.K., Shults, C.W., and Gage, F.H. (2002). The adult substantia nigra contains progenitor cells with neurogenic potential. J Neurosci 22, 6639-6649 .
70
Lim, D.A., and Alvarez-Buylla, A. (1999). Interaction between astrocytes and adult subventricular zone precursors stimulates neurogenesis. Proc Natl Acad Sci U S A 96, 7526-7531 . doi: 10.1073/pnas.96.13.7526
71
Lim, D.A., Tramontin, A.D., Trevejo, J.M., Herrera, D.G., García- Verdugo, J.M., and Alvarez-Buylla, A. (2000). Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28, 713-726 . doi: 10.1016/S0896-6273(00)00148-3
72
Liu, H., and Zhang, S.C. (2011). Specification of neuronal and glial subtypes from human pluripotent stem cells. Cell Mol Life Sci 68, 3995-4008 . doi: 10.1007/s00018-011-0770-y
73
Liu, X., Wang, Q., Haydar, T.F., and Bordey, A. (2005). Nonsynaptic GABA signaling in postnatal subventricular zone controls proliferation of GFAP-expressing progenitors. Nat Neurosci 8, 1179-1187 . doi: 10.1038/nn1522
74
Lois, C., and Alvarez-Buylla, A. (1993). Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. Proc Natl Acad Sci U S A 90, 2074-2077 . doi: 10.1073/pnas.90.5.2074
75
Lois, C., and Alvarez-Buylla, A. (1994). Long-distance neuronal migration in the adult mammalian brain. Science 264, 1145-1148 . doi: 10.1126/science.8178174
76
López-Toledano, M.A., and Shelanski, M.L. (2007). Increased neurogenesis in young transgenic mice overexpressing human APP(Sw, Ind). J Alzheimers Dis 12, 229-240 .
77
Lorson, C.L., and Androphy, E.J. (1998). The domain encoded by exon 2 of the survival motor neuron protein mediates nucleic acid binding. Hum Mol Genet 7, 1269-1275 . doi: 10.1093/hmg/7.8.1269
78
Lorson, C.L., Hahnen, E., Androphy, E.J., and Wirth, B. (1999). A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci U S A 96, 6307-6311 . doi: 10.1073/pnas.96.11.6307
79
Lorson, C.L., Strasswimmer, J., Yao, J.M., Baleja, J.D., Hahnen, E., Wirth, B., Le, T., Burghes, A.H., and Androphy, E.J. (1998). SMN oligomerization defect correlates with spinal muscular atrophy severity. Nat Genet 19, 63-66 . doi: 10.1038/ng0598-63
80
Lucassen, P.J., Stumpel, M.W., Wang, Q., and Aronica, E. (2010). Decreased numbers of progenitor cells but no response to antidepressant drugs in the hippocampus of elderly depressed patients. Neuropharmacology 58, 940-949 . doi: 10.1016/j.neuropharm.2010.01.012
81
Lugert, S., Basak, O., Knuckles, P., Haussler, U., Fabel, K., G?tz, M., Haas, C.A., Kempermann, G., Taylor, V., and Giachino, C. (2010). Quiescent and active hippocampal neural stem cells with distinct morphologies respond selectively to physiological and pathological stimuli and aging. Cell Stem Cell 6, 445-456 . doi: 10.1016/j.stem.2010.03.017
82
Luskin, M.B. (1993). Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 11, 173-189 . doi: 10.1016/0896-6273(93)90281-U
83
Maekawa, M., Takashima, N., Arai, Y., Nomura, T., Inokuchi, K., Yuasa, S., and Osumi, N. (2005). Pax6 is required for production and maintenance of progenitor cells in postnatal hippocampal neurogenesis. Genes Cells 10, 1001-1014 . doi: 10.1111/j.1365-2443.2005.00893.x
84
Marchetto, M.C., Carromeu, C., Acab, A., Yu, D., Yeo, G.W., Mu, Y., Chen, G., Gage, F.H., and Muotri, A.R. (2010a). A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 143, 527-539 . doi: 10.1016/j.cell.2010.10.016
85
Marchetto, M.C., Winner, B., and Gage, F.H. (2010b). Pluripotent stem cells in neurodegenerative and neurodevelopmental diseases. Hum Mol Genet 19, R71-R76 . doi: 10.1093/hmg/ddq159
86
Mejia-Gervacio, S., Murray, K., and Lledo, P.M. (2011). NKCC1 controls GABAergic signaling and neuroblast migration in the postnatal forebrain. Neural Dev 6, 4. doi: 10.1186/1749-8104-6-4
87
Méndez-Gómez, H.R., Verga?o-Vera, E., Abad, J.L., Bulfone, A., Moratalla, R., de Pablo, F., and Vicario-Abejón, C. (2011). The T-box brain 1 (Tbr1) transcription factor inhibits astrocyte formation in the olfactory bulb and regulates neural stem cell fate. Mol Cell Neurosci 46, 108-121 . doi: 10.1016/j.mcn.2010.08.011
88
Mira, H., Andreu, Z., Suh, H., Lie, D.C., Jessberger, S., Consiglio, A., San Emeterio, J., Hortigüela, R., Marqués-Torrejón, M.A., Nakashima, K., . (2010). Signaling through BMPR-IA regulates quiescence and long-term activity of neural stem cells in the adult hippocampus. Cell Stem Cell 7, 78-89 . doi: 10.1016/j.stem.2010.04.016
89
Morshead, C.M., Reynolds, B.A., Craig, C.G., McBurney, M.W., Staines, W.A., Morassutti, D., Weiss, S., and van der Kooy, D. (1994). Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells. Neuron 13, 1071-1082 . doi: 10.1016/0896-6273(94)90046-9
90
Mu, Y., Lee, S.W., and Gage, F.H. (2010). Signaling in adult neurogenesis. Curr Opin Neurobiol 20, 416-423 . doi: 10.1016/j.conb.2010.04.010
91
Muroyama, Y., Kondoh, H., and Takada, S. (2004). Wnt proteins promote neuronal differentiation in neural stem cell culture. Biochem Biophys Res Commun 313, 915-921 . doi: 10.1016/j.bbrc.2003.12.023
92
Muth-K?hne, E., Terhag, J., Pahl, S., Werner, M., Joshi, I., and Hollmann, M. (2010). Functional excitatory GABAA receptors precede ionotropic glutamate receptors in radial glia-like neural stem cells. Mol Cell Neurosci 43, 209-221 . doi: 10.1016/j.mcn.2009.11.002
93
Nacher, J., Varea, E., Blasco-Iba?ez, J.M., Castillo-Gomez, E., Crespo, C., Martinez-Guijarro, F.J., and McEwen, B.S. (2005). Expression of the transcription factor Pax 6 in the adult rat dentate gyrus. J Neurosci Res 81, 753-761 . doi: 10.1002/jnr.20596
94
Nácher, J., Varea, E., Miguel Blasco-Ibá?ez, J., Gómez-Climent, M.A., Castillo-Gómez, E., Crespo, C., Martínez-Guijarro, F.J., and McEwen, B.S. (2007). N-methyl-d-aspartate receptor expression during adult neurogenesis in the rat dentate gyrus. Neuroscience 144, 855-864 . doi: 10.1016/j.neuroscience.2006.10.021
95
O’Donovan, M.C., Craddock, N., Norton, N., Williams, H., Peirce, T., Moskvina, V., Nikolov, I., Hamshere, M., Carroll, L., Georgieva, L., , and the Molecular Genetics of Schizophrenia Collaboration. (2008). Identification of loci associated with schizophrenia by ge-nome-wide association and follow-up. Nat Genet 40, 1053-1055 . doi: 10.1038/ng.201
96
O’Keeffe, G.C., Barker, R.A., and Caldwell, M.A. (2009). Dopaminergic modulation of neurogenesis in the subventricular zone of the adult brain. Cell Cycle 8, 2888-2894 . doi: 10.4161/cc.8.18.9512
97
Pan, B., Huang, X.F., and Deng, C. (2011). Antipsychotic treatment and neuregulin 1-ErbB4 signalling in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 35, 924-930 . doi: 10.1016/j.pnpbp.2011.04.002
98
Parent, J.M., Jessberger, S., Gage, F.H., and Gong, C. (2007). Is neurogenesis reparative after status epilepticus? Epilepsia 48, 69-71 . doi: 10.1111/j.1528-1167.2007.01355.x
99
Park, I.H., Arora, N., Huo, H., Maherali, N., Ahfeldt, T., Shimamura, A., Lensch, M.W., Cowan, C., Hochedlinger, K., and Daley, G.Q. (2008). Disease-specific induced pluripotent stem cells. Cell 134, 877-886 . doi: 10.1016/j.cell.2008.07.041
100
Pedrosa,E., Sandler, V., Shah, A., Carroll, R., Chang, C., Rockowitz, S., Guo, X., Zheng, D., and Lachman, H.M. (2011). Development of patient-specific neurons in schizophrenia using induced pluripotent stem cells. J Neurogenet 25, 88-103 . doi: 10.3109/01677063.2011.597908
101
Peretto, P., Giachino, C., Aimar, P., Fasolo, A., and Bonfanti, L. (2005). Chain formation and glial tube assembly in the shift from neonatal to adult subventricular zone of the rodent forebrain. J Comp Neurol 487, 407-427 . doi: 10.1002/cne.20576
102
Peretto, P., Merighi, A., Fasolo, A., and Bonfanti, L. (1997). Glial tubes in the rostral migratory stream of the adult rat. Brain Res Bull 42, 9-21 . doi: 10.1016/S0361-9230(96)00116-5
103
Peretto, P., Merighi, A., Fasolo, A., and Bonfanti, L. (1999). The subependymal layer in rodents: a site of structural plasticity and cell migration in the adult mammalian brain. Brain Res Bull 49, 221-243 . doi: 10.1016/S0361-9230(99)00037-4
104
Pierfelice, T., Alberi, L., and Gaiano, N. (2011). Notch in the vertebrate nervous system: an old dog with new tricks. Neuron 69, 840-855 . doi: 10.1016/j.neuron.2011.02.031
105
Ponti, G., Aimar, P., and Bonfanti, L. (2006). Cellular composition and cytoarchitecture of the rabbit subventricular zone and its extensions in the forebrain. J Comp Neurol 498, 491-507 . doi: 10.1002/cne.21043
106
Ramírez-Castillejo, C., Sánchez-Sánchez, F., Andreu-Agulló, C., Ferrón, S.R., Aroca-Aguilar, J.D., Sánchez, P., Mira, H., Escribano, J., and Fari?as, I. (2006). Pigment epithelium-derived factor is a niche signal for neural stem cell renewal. Nat Neurosci 9, 331-339 . doi: 10.1038/nn1657
107
Reynolds, B.A., and Weiss, S. (1992). Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255, 1707-1710 . doi: 10.1126/science.1553558
108
Rietze, R., Poulin, P., and 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, 397-408 . doi: 10.1002/1096-9861(20000828)424:3<397::AID-CNE2>3.0.CO;2-A
109
Ripke, S., Sanders, A.R., Kendler, K.S., Levinson, D.F., Sklar, P., Holmans, P.A., Lin, D.Y., Duan, J., Ophoff, R.A., Andreassen, O.A., , and the Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium. (2011). Genome-wide association study identifies five new schizophrenia loci. Nat Genet 43, 969-976 . doi: 10.1038/ng.940
110
Rodríguez, J.J., Jones, V.C., Tabuchi, M., Allan, S.M., Knight, E.M., LaFerla, F.M., Oddo, S., and Verkhratsky,A. (2008). Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer’s disease. PLoS One 3, e2935. doi: 10.1371/journal.pone.0002935
111
Roy,N.S., Cleren, C., Singh, S.K., Yang, L., Beal, M.F., and Goldman, S.A. (2006). Functional engraftment of human ES cell-derived dopaminergic neurons enriched by coculture with telomerase- immortalized midbrain astrocytes. Nat Med 12, 1259-1268 . doi: 10.1038/nm1495
112
Roybon, L., Hjalt, T., Stott, S., Guillemot, F., Li, J.Y., and Brundin, P. (2009). Neurogenin2 directs granule neuroblast production and amplification while NeuroD1 specifies neuronal fate during hippocampal neurogenesis. PLoS One 4, e4779. doi: 10.1371/journal.pone.0004779
113
Samaco, R.C., Hogart, A., and LaSalle, J.M. (2005). Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. Hum Mol Genet 14, 483-492 . doi: 10.1093/hmg/ddi045
114
Schneider, B.L., Seehus, C.R., Capowski, E.E., Aebischer, P., Zhang, S.C., and Svendsen, C.N. (2007). Over-expression of alpha- synuclein in human neural progenitors leads to specific changes in fate and differentiation. Hum Mol Genet 16, 651-666 . doi: 10.1093/hmg/ddm008
115
Schulz-Schaeffer, W.J. (2010). The synaptic pathology of alpha- synuclein aggregation in dementia with Lewy bodies, Parkinson’s disease and Parkinson’s disease dementia. Acta Neuropathol 120, 131-143 . doi: 10.1007/s00401-010-0711-0
116
Segawa, M. (2001). Pathophysiology of Rett syndrome from the stand point of clinical characteristics. Brain Dev 23, S94-S98 . doi: 10.1016/S0387-7604(01)00352-7
117
Seki, T., and Arai, Y. (1993). 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, 2351-2358 .
Song, H.J., Stevens, C.F., and Gage, F.H. (2002b). Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons. Nat Neurosci 5, 438-445 .
125
Spitere, K., Toulouse, A., O’Sullivan, D.B., and Sullivan, A.M. (2008). TAT-PAX6 protein transduction in neural progenitor cells: a novel approach for generation of dopaminergic neurones in vitro. Brain Res 1208, 25-34 . doi: 10.1016/j.brainres.2008.02.065
126
Stefansson, H., Ophoff, R.A., Steinberg, S., Andreassen, O.A., Cichon, S., Rujescu, D., Werge, T., Pietil?inen, O.P., Mors, O., Mortensen, P.B., , and the Genetic Risk and Outcome in Psychosis (GROUP). (2009). Common variants conferring risk of schizophrenia. Nature 460, 744-747 .
127
Suh, H., Consiglio, A., Ray, J., Sawai, T., D’Amour, K.A., and Gage, F.H. (2007). In vivo fate analysis reveals the multipotent and self-renewal capacities of Sox2+ neural stem cells in the adult hippocampus. Cell Stem Cell 1, 515-528 . doi: 10.1016/j.stem.2007.09.002
128
Suh, H., Deng, W., and Gage, F.H. (2009). Signaling in adult neurogenesis. Annu Rev Cell Dev Biol 25, 253-275 . doi: 10.1146/annurev.cellbio.042308.113256
129
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., and Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872 . doi: 10.1016/j.cell.2007.11.019
130
Taranova, O.V., Magness, S.T., Fagan, B.M., Wu, Y., Surzenko, N., Hutton, S.R., and Pevny, L.H. (2006). SOX2 is a dose-dependent regulator of retinal neural progenitor competence. Genes Dev 20, 1187-1202 . doi: 10.1101/gad.1407906
131
Tattersfield, A.S., Croon, R.J., Liu, Y.W., Kells, A.P., Faull, R.L., and Connor, B. (2004). Neurogenesis in the striatum of the quinolinic acid lesion model of Huntington’s disease. Neuroscience 127, 319-332 . doi: 10.1016/j.neuroscience.2004.04.061
132
Toni, N., Teng, E.M., Bushong, E.A., Aimone, J.B., Zhao, C., Consiglio, A., van Praag, H., Martone, M.E., Ellisman, M.H., and Gage, F.H. (2007). Synapse formation on neurons born in the adult hippocampus. Nat Neurosci 10, 727-734 . doi: 10.1038/nn1908
133
Tozuka, Y., Fukuda, S., Namba, T., Seki, T., and Hisatsune, T. (2005). GABAergic excitation promotes neuronal differentiation in adult hippocampal progenitor cells. Neuron 47, 803-815 . doi: 10.1016/j.neuron.2005.08.023
134
van Praag, H., Schinder, A.F., Christie, B.R., Toni, N., Palmer, T.D., and Gage, F.H. (2002). Functional neurogenesis in the adult hippocampus. Nature 415, 1030-1034 . doi: 10.1038/4151030a
135
Vekrellis, K., Xilouri, M., Emmanouilidou, E., Rideout, H.J., and Stefanis, L. (2011). Pathological roles of α-synuclein in neurological disorders. Lancet Neurol 10, 1015-1025 . doi: 10.1016/S1474-4422(11)70213-7
136
Verret, L., Jankowsky, J.L., Xu, G.M., Borchelt, D.R., and Rampon, C. (2007). Alzheimer’s-type amyloidosis in transgenic mice impairs survival of newborn neurons derived from adult hippocampal neurogenesis. J Neurosci 27, 6771-6780 . doi: 10.1523/JNEUROSCI.5564-06.2007
Wegner, F., Kraft, R., Busse, K., Schaarschmidt, G., H?rtig, W., Schwarz, S.C., and Schwarz, J. (2009). Glutamate receptor properties of human mesencephalic neural progenitor cells: NMDA enhances dopaminergic neurogenesis in vitro. J Neurochem 111, 204-216 . doi: 10.1111/j.1471-4159.2009.06315.x
139
Wen, P.H., Hof, P.R., Chen, X., Gluck, K., Austin, G., Younkin, S.G., Younkin, L.H., DeGasperi, R., Gama Sosa, M.A., Robakis, N.K., . (2004). The presenilin-1 familial Alzheimer disease mutant P117L impairs neurogenesis in the hippocampus of adult mice. Exp Neurol 188, 224-237 . doi: 10.1016/j.expneurol.2004.04.002
140
Werning, M., Zhao, J.P., Pruszak, J., Hedlund, E., Fu, D., Soldner, F., Broccoli, V., Constantine-Paton, M., Isacson, O., and Jaenisch, R. (2008). Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc Natl Acad Sci USA 105, 5856-5861 . doi: 10.1073/pnas.0801677105
Yokley, J.L., Prasad, K.M., Chowdari, K.V., Talkowski, M.E., Wood, J., Gur, R.C., Gur, R.E., Almasy, L., Nimgaonkar, V.L., and Pogue-Geile, M.F. (2011). Genetic associations between neuregulin-1 SNPs and neurocognitive function in multigenerational, multiplex schizophrenia families. Psychiatr Genet . 2012Dec21. [Epub ahead of print]
144
Yoneyama, M., Nakamichi, N., Fukui, M., Kitayama, T., Georgiev, D.D., Makanga, J.O., Nakamura, N., Taniura, H., and Yoneda, Y. (2008). Promotion of neuronal differentiation through activation of N-methyl-D-aspartate receptors transiently expressed by undifferentiated neural progenitor cells in fetal rat neocortex. J Neurosci Res 86, 2392-2402 . doi: 10.1002/jnr.21696
145
Yoshinaga, Y., Kagawa, T., Shimizu, T., Inoue, T., Takada, S., Kuratsu, J., and Taga, T. (2010). Wnt3a promotes hippocampal neurogenesis by shortening cell cycle duration of neural progenitor cells. Cell Mol Neurobiol 30, 1049-1058 . doi: 10.1007/s10571-010-9536-6
146
Yu, J., Vodyanik, M.A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J.L., Tian, S., Nie, J., Jonsdottir, G.A., Ruotti, V., Stewart, R., . (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917-1920 . doi: 10.1126/science.1151526
147
Yuan, L., Zhou, X., Li, D., Ma, W., Yu, H., Xi, Y., and Xiao, R. (2012). Pattern recognition receptors involved in the inflammatory attenuating effects of soybean isoflavone in β-amyloid peptides 1-42 treated rats. Neurosci Lett 506, 266-270 . doi: 10.1016/j.neulet.2011.11.020
148
Zhang, C., McNeil, E., Dressler, L., and Siman, R. (2007). Long- lasting impairment in hippocampal neurogenesis associated with amyloid deposition in a knock-in mouse model of familial Alzheimer’s disease. Exp Neurol 204, 77-87 . doi: 10.1016/j.expneurol.2006.09.018
149
Zhao, C., Deng, W., and Gage, F.H. (2008). Mechanisms and functional implications of adult neurogenesis. Cell 132, 645-660 . doi: 10.1016/j.cell.2008.01.033
