Abstract
Recent progress in biology has shown that many if not all adult tissues contain a population of stem cells. It is believed that these cells are involved in the regeneration of the tissue or organ in which they reside as a response to the natural turnover of differentiated cells or to injury. In the adult mammalian brain, stem cells in the subventricular zone and the dentate gyrus may also play a role in the replacement of neurons. A positive beneficial response to injury does not necessarily require cell replacement. New findings suggest that some populations of endogenous neural stem cells in the central nervous system may have adopted a function different from cell replacement and are involved in the protection of neurons in diverse paradigms of disease and injury. In this article, we will focus on the immature cell populations of the central nervous system and the signal transduction pathways that regulate them which suggest new possibilities for their manipulation in injury and disease.
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McKay R, Kittappa R (2008) Neuron 58:659–661
Kordower JH, Chu Y, Hauser RA, Freeman TB, Olanow CW (2008) Nat Med 14:504–506
Li JY, Englund E, Holton JL, Soulet D, Hagell P, Lees AJ, Lashley T, Quinn NP, Rehncrona S, Bjorklund A, Widner H, Revesz T, Lindvall O, Brundin P (2008) Nat Med 14:501–503
Yamanaka K, Boillee S, Roberts EA, Garcia ML, McAlonis-Downes M, Mikse OR, Cleveland DW, Goldstein LS (2008) Proc Natl Acad Sci USA 105:7594–7599
Amariglio N, Hirshberg A, Scheithauer BW, Cohen Y, Loewenthal R, Trakhtenbrot L, Paz N, Koren-Michowitz M, Waldman D, Leider-Trejo L, Toren A, Constantini S, Rechavi G (2009) PLoS Med 6:e1000029
Altman J, Das GD (1965) J Comp Neurol 124:319–335
Schlessinger AR, Cowan WM, Gottlieb DI (1975) J Comp Neurol 159:149–175
Kaplan MS, Bell DH (1984) J Neurosci 4:1429–1441
Privat A, Drian MJ (1975) Brain Res 88:518–524
Vaysse PJ, Goldman JE (1990) Neuron 5:227–235
Levison SW, Goldman JE (1993) Neuron 10:201–212
Cameron HA, Woolley CS, McEwen BS, Gould E (1993) Neuroscience 56:337–344
Luskin MB (1993) Neuron 11:173–189
Lois C, Alvarez-Buylla A (1993) Proc Natl Acad Sci USA 90:2074–2077
Kuhn HG, Dickinson-Anson H, Gage FH (1996) J Neurosci 16:2027–2033
Palmer TD, Takahashi J, Gage FH (1997) Mol Cell Neurosci 8:389–404
Palmer TD, Ray J, Gage FH (1995) Mol Cell Neurosci 6:474–486
Marmur R, Mabie PC, Gokhan S, Song Q, Kessler JA, Mehler MF (1998) Dev Biol 204:577–591
Ourednik J, Ourednik V, Lynch WP, Schachner M, Snyder EY (2002) Nat Biotechnol 20:1103–1110
Androutsellis-Theotokis A, Leker RR, Soldner F, Hoeppner DJ, Ravin R, Poser SW, Rueger MA, Bae SK, Kittappa R, McKay RD (2006) Nature 442:823–826
Temple S (1989) Nature 340:471–473
Hockfield S, McKay RD (1985) J Neurosci 5:3310–3328
Lendahl U, Zimmerman LB, McKay RD (1990) Cell 60:585–595
Cattaneo E, McKay R (1990) Nature 347:762–765
Reynolds BA, Weiss S (1992) Science 255:1707–1710
Taupin P, Gage FH (2002) J Neurosci Res 69:745–749
Morshead CM, Reynolds BA, Craig CG, McBurney MW, Staines WA, Morassutti D, Weiss S, van der Kooy D (1994) Neuron 13:1071–1082
Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A (1999) Cell 97:703–716
D’Amour KA, Gage FH (2003) Proc Natl Acad Sci USA 100(Suppl 1):11866–11872
Pevny LH, Nicolis SK (2010) Int J Biochem Cell Biol 42:421–424
Ahn S, Joyner AL (2005) Nature 437:894–897
Jackson EL, Garcia-Verdugo JM, Gil-Perotin S, Roy M, Quinones-Hinojosa A, VandenBerg S, Alvarez-Buylla A (2006) Neuron 51:187–199
Sakakibara S, Imai T, Hamaguchi K, Okabe M, Aruga J, Nakajima K, Yasutomi D, Nagata T, Kurihara Y, Uesugi S, Miyata T, Ogawa M, Mikoshiba K, Okano H (1996) Dev Biol 176:230–242
Temple S, Raff MC (1985) Nature 313:223–225
Androutsellis-Theotokis A, Rueger MA, Park DM, Mkhikian H, Korb E, Poser SW, Walbridge S, Munasinghe J, Koretsky AP, Lonser RR, McKay RD (2009) Proc Natl Acad Sci USA 106:13570–13575
Basak O, Taylor V (2007) Eur J Neurosci 25:1006–1022
Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, Olweus J, Kearney J, Buck DW (1997) Blood 90:5002–5012
Uchida N, Buck DW, He D, Reitsma MJ, Masek M, Phan TV, Tsukamoto AS, Gage FH, Weissman IL (2000) Proc Natl Acad Sci USA 97:14720–14725
Bull ND, Bartlett PF (2005) J Neurosci 25:10815–10821
Lee A, Kessler JD, Read TA, Kaiser C, Corbeil D, Huttner WB, Johnson JE, Wechsler-Reya RJ (2005) Nat Neurosci 8:723–729
Pekcec A, Loscher W, Potschka H (2006) Neuroreport 17:571–574
Wang YZ, Plane JM, Jiang P, Zhou CJ, Deng W (2011) Stem Cells 29:907–912
Lin RC, Matesic DF, Marvin M, McKay RD, Brustle O (1995) Neurobiol Dis 2:79–85
Clarke SR, Shetty AK, Bradley JL, Turner DA (1994) Neuroreport 5:1885–1888
Ourednik V, Ourednik J, Flax JD, Zawada WM, Hutt C, Yang C, Park KI, Kim SU, Sidman RL, Freed CR, Snyder EY (2001) Science 293:1820–1824
Androutsellis-Theotokis A, Rueger MA, Mkhikian H, Korb E, McKay RD (2008) Cold Spring Harb Symp Quant Biol 73:403–410
Wexler E, Palmer T (2002) Trends Neurosci 25:225–227
Klein C, Butt SJ, Machold RP, Johnson JE, Fishell G (2005) Development 132:4497–4508
Merkle FT, Mirzadeh Z, Alvarez-Buylla A (2007) Science 317:381–384
Alvarez-Buylla A, Kohwi M, Nguyen TM, Merkle FT (2008) Cold Spring Harb Symp Quant Biol 73:357–365
Magavi SS, Leavitt BR, Macklis JD (2000) Nature 405:951–955
Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O (2002) Nat Med 8:963–970
Curtis MA, Penney EB, Pearson AG, van Roon-Mom WM, Butterworth NJ, Dragunow M, Connor B, Faull RL (2003) Proc Natl Acad Sci USA 100:9023–9027
Jin K, Peel AL, Mao XO, Xie L, Cottrell BA, Henshall DC, Greenberg DA (2004) Proc Natl Acad Sci USA 101:343–347
Liu J, Solway K, Messing RO, Sharp FR (1998) J Neurosci 18:7768–7778
Zhang RL, Zhang ZG, Chopp M (2008) Neuropharmacology 55:345–352
Kuhn HG, Winkler J, Kempermann G, Thal LJ, Gage FH (1997) J Neurosci 17:5820–5829
Martens DJ, Seaberg RM, van der Kooy D (2002) Eur J Neurosci 16:1045–1057
Holmberg J, Armulik A, Senti KA, Edoff K, Spalding K, Momma S, Cassidy R, Flanagan JG, Frisen J (2005) Genes Dev 19:462–471
Craig CG, Tropepe V, Morshead CM, Reynolds BA, Weiss S, van der Kooy D (1996) J Neurosci 16:2649–2658
Nakatomi H, Kuriu T, Okabe S, Yamamoto S, Hatano O, Kawahara N, Tamura A, Kirino T, Nakafuku M (2002) Cell 110:429–441
Jiao JW, Feldheim DA, Chen DF (2008) Proc Natl Acad Sci USA 105:8778–8783
Lie DC, Colamarino SA, Song HJ, Desire L, Mira H, Consiglio A, Lein ES, Jessberger S, Lansford H, Dearie AR, Gage FH (2005) Nature 437:1370–1375
Ehm O, Goritz C, Covic M, Schaffner I, Schwarz TJ, Karaca E, Kempkes B, Kremmer E, Pfrieger FW, Espinosa L, Bigas A, Giachino C, Taylor V, Frisen J, Lie DC (2010) J Neurosci 30:13794–13807
Gould E, Reeves AJ, Graziano MS, Gross CG (1999) Science 286:548–552
Chen Y, Ai Y, Slevin JR, Maley BE, Gash DM (2005) Exp Neurol 196:87–95
Chen J, Magavi SS, Macklis JD (2004) Proc Natl Acad Sci USA 101:16357–16362
Cooper O, Isacson O (2004) J Neurosci 24:8924–8931
Fallon J, Reid S, Kinyamu R, Opole I, Opole R, Baratta J, Korc M, Endo TL, Duong A, Nguyen G, Karkehabadhi M, Twardzik D, Patel S, Loughlin S (2000) Proc Natl Acad Sci USA 97:14686–14691
Jin K, LaFevre-Bernt M, Sun Y, Chen S, Gafni J, Crippen D, Logvinova A, Ross CA, Greenberg DA, Ellerby LM (2005) Proc Natl Acad Sci USA 102:18189–18194
Jin K, Minami M, Lan JQ, Mao XO, Batteur S, Simon RP, Greenberg DA (2001) Proc Natl Acad Sci USA 98:4710–4715
Jin K, Zhu Y, Sun Y, Mao XO, Xie L, Greenberg DA (2002) Proc Natl Acad Sci USA 99:11946–11950
Jin K, Mao XO, Sun Y, Xie L, Greenberg DA (2002) J Clin Invest 110:311–319
Kizil C, Kaslin J, Kroehne V, Brand M (2012) Dev Neurobiol 72(3):429–461
Chapouton P, Jagasia R, Bally-Cuif L (2007) Bioessays 29:745–757
Berg DA, Kirkham M, Beljajeva A, Knapp D, Habermann B, Ryge J, Tanaka EM, Simon A (2010) Development 137:4127–4134
Ryu JK, Cho T, Wang YT, McLarnon JG (2009) J Neuroinflammation 6:39
Martino G, Pluchino S, Bonfanti L, Schwartz M (2011) Physiol Rev 91:1281–1304
Hirsch EC, Hunot S (2009) Lancet Neurol 8:382–397
Salomoni P, Calegari F (2010) Trends Cell Biol 20:233–243
Androutsellis-Theotokis A, Walbridge S, Park DM, Lonser RR, McKay RD (2010) PLoS One 5:e10841
Meletis K, Wirta V, Hede SM, Nister M, Lundeberg J, Frisen J (2006) Development 133:363–369
Heitzler P, Simpson P (1991) Cell 64:1083–1092
Cagan RL, Ready DF (1989) Genes Dev 3:1099–1112
Simpson P (1990) Development 109:509–519
Cabrera CV (1990) Development 110:733–742
Artavanis-Tsakonas S, Rand MD, Lake RJ (1999) Science 284:770–776
Imayoshi I, Kageyama R (2011) Mol Neurobiol 44:7–12
Pierfelice TJ, Schreck KC, Eberhart CG, Gaiano N (2008) Cold Spring Harb Symp Quant Biol 73:367–375
Louvi A, Artavanis-Tsakonas S (2006) Nat Rev Neurosci 7:93–102
Ruohola H, Bremer KA, Baker D, Swedlow JR, Jan LY, Jan YN (1991) Cell 66:433–449
Greenwald I, Rubin GM (1992) Cell 68:271–281
Spana EP, Doe CQ (1996) Neuron 17:21–26
Campos-Ortega JA, Jan YN (1991) Annu Rev Neurosci 14:399–420
Kidd S, Kelley MR, Young MW (1986) Mol Cell Biol 6:3094–3108
Chiba S (2006) Stem Cells 24:2437–2447
Haddon C, Smithers L, Schneider-Maunoury S, Coche T, Henrique D, Lewis J (1998) Development 125:359–370
Morrison SJ, Perez SE, Qiao Z, Verdi JM, Hicks C, Weinmaster G, Anderson DJ (2000) Cell 101:499–510
Tanigaki K, Nogaki F, Takahashi J, Tashiro K, Kurooka H, Honjo T (2001) Neuron 29:45–55
Justice NJ, Jan YN (2002) Curr Opin Neurobiol 12:64–70
Stump G, Durrer A, Klein AL, Lutolf S, Suter U, Taylor V (2002) Mech Dev 114:153–159
Kamakura S, Oishi K, Yoshimatsu T, Nakafuku M, Masuyama N, Gotoh Y (2004) Nat Cell Biol 6:547–554
Taylor MK, Yeager K, Morrison SJ (2007) Development 134:2435–2447
Levy DE, Darnell JE Jr (2002) Nat Rev Mol Cell Biol 3:651–662
Kiuchi N, Nakajima K, Ichiba M, Fukada T, Narimatsu M, Mizuno K, Hibi M, Hirano T (1999) J Exp Med 189:63–73
Niwa H, Burdon T, Chambers I, Smith A (1998) Genes Dev 12:2048–2060
Bonni A, Sun Y, Nadal-Vicens M, Bhatt A, Frank DA, Rozovsky I, Stahl N, Yancopoulos GD, Greenberg ME (1997) Science 278:477–483
Johe KK, Hazel TG, Muller T, Dugich-Djordjevic MM, McKay RD (1996) Genes Dev 10:3129–3140
Song MR, Ghosh A (2004) Nat Neurosci 7:229–235
Rajan P, McKay RD (1998) J Neurosci 18:3620–3629
Androutsellis-Theotokis A, Rueger MA, Park DM, Boyd JD, Padmanabhan R, Campanati L, Stewart CV, LeFranc Y, Plenz D, Walbridge S, Lonser RR, McKay RD (2010) PLoS One 5:e9414
Hatakeyama J, Bessho Y, Katoh K, Ookawara S, Fujioka M, Guillemot F, Kageyama R (2004) Development 131:5539–5550
Woo DH, Kim SK, Lim HJ, Heo J, Park HS, Kang GY, Kim SE, You HJ, Hoeppner DJ, Kim Y, Kwon H, Choi TH, Lee JH, Hong SH, Song KW, Ahn EK, Chenoweth JG, Tesar PJ, McKay RD, Kim JH (2012) Gastroenterology 142:602–611
Acknowledgments
The work was supported by the Else Kröner-Fresenius-Stiftung and the Centre for Regenerative Therapies, Dresden (AA-T) and the European Commission Project NeuroStemcell (RK).
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Kittappa, R., Bornstein, S.R. & Androutsellis-Theotokis, A. The Role of eNSCs in Neurodegenerative Disease. Mol Neurobiol 46, 555–562 (2012). https://doi.org/10.1007/s12035-012-8303-8
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DOI: https://doi.org/10.1007/s12035-012-8303-8