Introduction: There is a nondeveloped neurogenic potential in the adult mammalian brain, which could be the basis for neuroregenerative strategies. Many research efforts have been made to understand the control mechanisms which regulate the transition from a neural precursor to a neuron in the adult brain. Embryonic cerebrospinal fluid (CSF) is a complex fluid which has been shown to play a key role in neural precursor behavior during development, working as a powerful neurogenic inductor. We tested if the neurogenic properties of embryonic CSF are able to increase the neurogenic activity of neuronal precursors from the subventricular zone (SVZ) in the brains of adult mice. Results: Our results show that mouse embryonic CSF significantly increases the neurogenic activity in precursor cells from adult brain SVZ. This intense neurogenic effect was specific for embryonic CSF and was not induced by adult CSF. Conclusions: Embryonic CSF is a powerful neurogenesis inductor in homologous neuronal precursors in the adult brain. This property of embryonic CSF could be a useful tool in neuroregeneration strategies.

Keywords:
Embryonic cerebrospinal fluid, Subventricular zone, Neuronal precursors, Adult brain, Neurogenesis
1.
Alonso, M.I., C. Martin, E. Carnicero, D. Bueno, A. Gato (2011) Cerebrospinal fluid control of neurogenesis induced by retinoic acid during early brain development. Dev Dyn 240: 1650-1659.
2.
Arias-Carríon, O., T. Olivares-Banuelos, R. Drucker-Colin (2007) Neurogenesis in the adult brain. Revist Neurol 44: 541-550.
3.
Buddensiek, J., A. Dressel, M. Kowalski, A. Storch, M. Sabolek (2009) Adult cerebrospinal fluid inhibits neurogenesis but facilitates gliogenesis from fetal rat neural stem cells. J Neurosci Res 87: 3054-3066.
4.
Christie, K., A.M. Turnley (2013) Regulation of endogenous neural stem/progenitor cells for neural repair-factors that promote neurogenesis and gliogenesis in the normal and damaged brain. Front Cell Neurosci 6: 70.
5.
Diez del Corral, R., K.G. Storey (2001) Markers in vertebrate neurogenesis. Nat Rev Neurosci 2: 835-839.
6.
Gato, A., M.E. Desmond (2009) Why the embryo still matters: CSF and the neuroepithelium as interdependent regulators of embryonic brain growth, morphogenesis and histiogenesis. Dev Biol 327: 263-272.
7.
Gato, A., P. Martin, M.I. Alonso, C. Martin, M.A. Pulgar, J.A. Moro (2004) Analysis of cerebro-spinal fluid protein composition in early developmental stages in chick embryos. J Exp Zool A Comp Exp Biol 301A: 280-289.
8.
Gato, A., J.A. Moro, M.I. Alonso, D. Bueno, A. De la Mano, C. Martin (2005) Embryonic cerebrospinal fluid regulates neuroepithelial survival, proliferation, and neurogenesis in chick embryos. Anat Rec A Discov Mol Cell Evol Biol 284A: 475-484.
9.
Haskell, G.T., A.S. La Mantia (2005) Retinoic acid signaling identifies a distinct precursor population in the developing and adult forebrain. J. Neurosci 25: 7636-7647.
10.
Ihrie, R.A., A. Alvarez-Buylla (2011) Lake-front property: a unique germinal niche by the lateral ventricles of the adult brain. Neuron 70: 674-686.
11.
Kaneko N., E. Kako, K. Sawamoto (2011) Prospects and limitations of using endogenous neural stem cells for brain regeneration. Genes 2: 107-130.
12.
Kaneko, N., K. Sawamoto (2009) Adult neurogenesis and its alteration under pathological conditions. Neurosci Res 63: 155-164.
13.
Kazanis, I., J. Lathia, L. Moss, C. ffrench-Constant (2008) The neural stem cell microenvironment; in Scadden, D. (ed): StemBook. Cambridge, Mass., Stem Cell Research Community.
14.
Kernie, S.G., J.M. Parent (2010) Forebrain neurogenesis after focal ischemic and traumatic brain injury. Neurobiol Dis 37: 267-274.
15.
Kriegstein, A., A. Alvarez-Buylla (2009) The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci 32: 149-184.
16.
Kuhn, H.G., K. Blomgren (2011) Developmental dysregulation of adult neurogenesis. Eur J Neurosci 33: 1115-1122.
17.
Lathia, J.D., M.S. Rao, M.P. Mattson, C. Ffrench-Constant (2007) The microenvironment of the embryonic neural stem cell: lessons from adult niches? Dev Dyn 236: 3267-3282.
18.
Lehtinen, M.K., C.A. Walsh (2011) Neurogenesis at the brain-cerebrospinal fluid interface. Annu Rev Cell Dev Biol 27: 653-679.
19.
Liu, L., K. Duff (2008) A technique for serial collection of cerebrospinal fluid from the cisterna magna in mouse. J Vis Exp DOI: 960.10.3791/960.
20.
Martín, C., M.I. Alonso, C. Santiago, J.A. Moro, A. De la Mano, R. Carretero, A. Gato (2009) Early embryonic brain development in rats requires the trophic influence of cerebrospinal fluid. Int J Dev Neurosci 27: 733-740.
21.
Martín, C., D. Bueno, M.I. Alonso, J.A. Moro, S. Callejo, C. Parada, P. Martin, E. Carnicero, A. Gato (2006) FGF2 plays a key role in embryonic cerebrospinal fluid trophic properties over chick embryo neuroepithelial stem cells. Dev Biol 297: 402-416.
22.
McCaffery, P. (2006) Retinoic acid regulates neurogenesis in the hippocampus - possible consequences for depression. Int J Neuropsychopharmacol 9: S79-S80.
23.
McCaffery, P.J., J. Adams, M. Maden, E. Rosa-Molinar (2003) Too much of a good thing: retinoic acid as an endogenous regulator of neural differentiation and exogenous teratogen. Eur J Neurosci 18: 457-472.
24.
McCaffery, P., U.C. Dräger (2000) Regulation of retinoic acid signaling in the embryonic nervous system: a master differentiation factor. Cytokine Growth Factor Rev 11: 233-249.
25.
Merkle, F.T., A. Alvarez-Buylla (2006) Neural stem cells in mammalian development. Curr Opin Cell Biol 18: 704-709.
26.
Miyan, J.A., M. Zendah, F. Mashayekhi, P.J. Owen-Lynch (2006) Cerebrospinal fluid supports viability and proliferation of cortical cells in vitro, mirroring in vivo development. Cerebrospinal Fluid Res 3: 2.
27.
Okano, H., K. Sawamoto (2008) Neural stem cells: involvement in adult neurogenesis and CNS repair. Philos Trans R Soc Lond B Biol Sci 363: 2111-2122.
28.
Panchision, D.M., R.D.G. McKay (2002) The control of neural stem cells by morphogenic signals. Curr Opin Genet Dev 12: 478-487.
29.
Parada, C., J. Carles Escola-Gil, D. Bueno (2008a) Low-density lipoproteins from embryonic cerebrospinal fluid are required for neural differentiation. J Neurosci Res 86: 2674-2684.
30.
Parada, C., A. Gato, M. Aparicio, D. Bueno (2006) Proteome analysis of chick embryonic cerebrospinal fluid. Proteomics 6: 312-320.
31.
Parada, C., A. Gato, D. Bueno (2005) Mammalian embryonic cerebrospinal fluid proteome has greater apolipoprotein and enzyme pattern complexity than the avian proteome. J Proteome Res 4: 2420-2428.
32.
Parada, C., A. Gato, D. Bueno (2008b) All-trans retinol and retinol-binding protein from embryonic cerebrospinal fluid exhibit dynamic behaviour during early central nervous system development. Neuroreport 19: 945-950.
33.
Sawada, M., K. Sawamoto (2013) Mechanisms of neurogenesis in the normal and injured adult brain. Keio J Med 62: 13-28.
34.
Sawamoto, K., H. Wichterle, O. Gonzalez-Perez, J.A. Cholfin, M. Yamada, N. Spassky, N.S. Murcia, J.M. Garcia-Verdugo, O. Marin, J.L.R. Rubenstein, M. Tessier-Lavigne, H. Okano, A. Alvarez-Buylla (2006) New neurons follow the flow of cerebrospinal fluid in the adult brain. Science 311: 629-632.
35.
Wang, H.F., F.C. Liu (2005) Regulation of multiple dopamine signal transduction molecules by retinoids in the developing striatum. Neuroscience 134: 97-105.
36.
Zappaterra, M.W., M.K. Lehtinen (2012) The cerebrospinal fluid: regulator of neurogenesis, behavior, and beyond. Cell Mol Life Sci 69: 2863-2878.
37.
Zhang, X.D., K.M. Klueber, Z.F. Guo, J. Cai, C.L. Lu, W.I. Winstead, M.S. Qiu, F.J. Roisen (2006) Induction of neuronal differentiation of adult human olfactory neuroepithelial-derived progenitors. Brain Res 1073: 109-119.
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2014
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