Skip to main content
SpringerLink
Log in

Ventral Mesencephalon Astrocytes Are More Efficient Than Those of Other Regions in Inducing Dopaminergic Neurons Through Higher Expression Level of TGF-β3

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Being supportive cells for neurons in the central nervous system, astrocytes have recently found to be associated with neurogenesis. Ventral mesencephalon (VM) astrocytes were also detected being instructive for VM dopaminergic (DA) neurogenesis, but the underling mechanisms are still unclear. This research is to figure out whether VM astrocytes are more efficient than those from other brain regions in inducing VM DA neurons from their precursors and whether transforming growth factor-βs (TGF-βs) are the underlying molecules. We found that, compared with astrocytes preparations from striatum and hippocampus, VM astrocytes preparations displayed markedly higher efficacy in inducing DA neurogenesis. Besides, they also expressed higher level of TGF-β3 than those of two other regions. When TGF-β3 gene expression in astrocytes preparations was inhibited by its antisense oligonucleotide, the induction of DA neurons decreased to a similar level among these three astrocytes preparations. Thus, our experiment indicates that VM astrocytes preparations which contained highly purified astrocytes are more efficient in inducing DA neurogenesis than those from other regions. Furthermore, it also suggests that the regional differences are regulated by different expression levels of TGF-β3 in those astrocytes preparations from different derivations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Banker, G. A. (1980). Trophic interactions between astroglial cells and hippocampal neurons in culture. Science, 209, 809–810. doi:10.1126/science.7403847.

    Article  PubMed  CAS  Google Scholar 

  • Castelo-Branco, G., & Arenas, E. (2006). Function of Wnts in dopaminergic neuron development. Neuro-Degenerative Diseases, 3, 5–11. doi:10.1159/000092086.

    Article  PubMed  CAS  Google Scholar 

  • Castelo-Branco, G., Sousa, K. M., Bryja, V., Pinto, L., Wagner, J., & Arenas, E. (2006). Ventral midbrain glia express region-specific transcription factors and regulate dopaminergic neurogenesis through Wnt-5a secretion. Molecular and Cellular Neurosciences, 31, 251–262. doi:10.1016/j.mcn.2005.09.014.

    Article  PubMed  CAS  Google Scholar 

  • Close, J. L., Gumuscu, B., & Reh, T. A. (2005). Retinal neurons regulate proliferation of postnatal progenitors and Muller glia in the rat retina via TGF beta signaling. Development, 132, 3015–3026. doi:10.1242/dev.01882.

    Article  PubMed  CAS  Google Scholar 

  • De, A., Hentges, S., Boyadjieva, N., & Sarkar, D. K. (2001). Effect of antisense suppression of transforming growth factor-beta3 gene on lactotropic cell proliferation. Journal of Neuroendocrinology, 13, 324–327. doi:10.1046/j.1365-2826.2001.00619.x.

    Article  PubMed  CAS  Google Scholar 

  • Doetsch, F. (2003). The glial identity of neural stem cells. Nature Neuroscience, 6, 1127–1134. doi:10.1038/nn1144.

    Article  PubMed  CAS  Google Scholar 

  • Doetsch, F., Caille, I., Lim, D. A., Garcia-Verdugo, J. M., & varez-Buylla, A. (1999). Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell, 97, 703–716. doi:10.1016/S0092-8674(00)80783-7.

    Article  PubMed  CAS  Google Scholar 

  • Engele, J., Schubert, D., & Bohn, M. C. (1991). Conditioned media derived from glial cell lines promote survival and differentiation of dopaminergic neurons in vitro: Role of mesencephalic glia. Journal of Neuroscience Research, 30, 359–371. doi:10.1002/jnr.490300212.

    Article  PubMed  CAS  Google Scholar 

  • Farkas, L. M., Dunker, N., Roussa, E., Unsicker, K., & Krieglstein, K. (2003). Transforming growth factor-beta(s) are essential for the development of midbrain dopaminergic neurons in vitro and in vivo. The Journal of Neuroscience, 23, 5178–5186.

    PubMed  CAS  Google Scholar 

  • Flanders, K. C., Ludecke, G., Engels, S., Cissel, D. S., Roberts, A. B., Kondaiah, P., et al. (1991). Localization and actions of transforming growth factor-beta s in the embryonic nervous system. Development, 113, 183–191.

    PubMed  CAS  Google Scholar 

  • Funahashi, J., Okafuji, T., Ohuchi, H., Noji, S., Tanaka, H., & Nakamura, H. (1999). Role of Pax-5 in the regulation of a mid-hindbrain organizer’s activity. Development, Growth & Differentiation, 41, 59–72. doi:10.1046/j.1440-169x.1999.00401.x.

    Article  CAS  Google Scholar 

  • Gomes dos Santos, A. L., Bochot, A., Tsapis, N., Artzner, F., Bejjani, R. A., Thillaye-Goldenberg, B., et al. (2006). Oligonucleotide-polyethylenimine complexes targeting retinal cells: Structural analysis and application to anti-TGFbeta-2 therapy. Pharmaceutical Research, 23, 770–781. doi:10.1007/s11095-006-9748-0.

    Article  PubMed  CAS  Google Scholar 

  • Hall, A. C., Mira, H., Wagner, J., & Arenas, E. (2003). Region-specific effects of glia on neuronal induction and differentiation with a focus on dopaminergic neurons. Glia, 43, 47–51. doi:10.1002/glia.10229.

    Article  PubMed  Google Scholar 

  • Hirsch, E., Graybiel, A. M., & Agid, Y. A. (1988). Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson’s disease. Nature, 334, 345–348. doi:10.1038/334345a0.

    Article  PubMed  CAS  Google Scholar 

  • Joannides, A., Gaughwin, P., Schwiening, C., Majed, H., Sterling, J., & Compston, A. (2004). Efficient generation of neural precursors from adult human skin: Astrocytes promote neurogenesis from skin-derived stem cells. Lancet, 364, 172–178. doi:10.1016/S0140-6736(04)16630-0.

    Article  PubMed  CAS  Google Scholar 

  • Kim, J. Y., Koh, H. C., Lee, J. Y., Chang, M. Y., Kim, Y. C., & Chung, H. Y. (2003). Dopaminergic neuronal differentiation from rat embryonic neural precursors by Nurr1 overexpression. Journal of Neurochemistry, 85, 1443–1454. doi:10.1046/j.1471-4159.2003.01780.x.

    Article  PubMed  CAS  Google Scholar 

  • Kornyei, Z., Szlavik, V., Szabo, B., Gocza, E., Czirok, A., & Madarasz, E. (2005). Humoral and contact interactions in astroglia/stem cell co-cultures in the course of glia-induced neurogenesis. Glia, 49, 430–444. doi:10.1002/glia.20123.

    Article  PubMed  Google Scholar 

  • Laywell, E. D., Rakic, P., Kukekov, V. G., Holland, E. C., & Steindler, D. A. (2000). Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain. Proceedings of the National Academy of Sciences of the United States of America, 97, 13883–13888. doi:10.1073/pnas.250471697.

    Article  PubMed  CAS  Google Scholar 

  • Lim, D. A., & varez-Buylla, A. (1999). Interaction between astrocytes and adult subventricular zone precursors stimulates neurogenesis. Proceedings of the National Academy of Sciences of the United States of America, 96, 7526–7531. doi:10.1073/pnas.96.13.7526.

    Article  PubMed  CAS  Google Scholar 

  • Lledo, P. M., Alonso, M., & Grubb, M. S. (2006). Adult neurogenesis and functional plasticity in neuronal circuits. Nature Reviews. Neuroscience, 7, 179–193. doi:10.1038/nrn1867.

    Article  PubMed  CAS  Google Scholar 

  • Meltzer, H. Y., & Stahl, S. M. (1976). The dopamine hypothesis of schizophrenia: A review. Schizophrenia Bulletin, 2, 19–76.

    PubMed  CAS  Google Scholar 

  • Nakayama, T., Momoki-Soga, T., & Inoue, N. (2003). Astrocyte-derived factors instruct differentiation of embryonic stem cells into neurons. Neuroscience Research, 46, 241–249.

    PubMed  CAS  Google Scholar 

  • O’Malley, E. K., Sieber, B. A., Black, I. B., & Dreyfus, C. F. (1992). Mesencephalic type I astrocytes mediate the survival of substantia nigra dopaminergic neurons in culture. Brain Research, 582, 65–70. doi:10.1016/0006-8993(92)90317-3.

    Article  PubMed  CAS  Google Scholar 

  • Patapoutian, A., & Reichardt, L. F. (2000). Roles of Wnt proteins in neural development and maintenance. Current Opinion in Neurobiology, 10, 392–399. doi:10.1016/S0959-4388(00)00100-8.

    Article  PubMed  CAS  Google Scholar 

  • Pixley, S. K. (1992). CNS glial cells support in vitro survival, division, and differentiation of dissociated olfactory neuronal progenitor cells. Neuron, 8, 1191–1204. doi:10.1016/0896-6273(92)90139-5.

    Article  PubMed  CAS  Google Scholar 

  • Qian, X., Shen, Q., Goderie, S. K., He, W., Capela, A., & Davis, A. A. (2000). Timing of CNS cell generation: a programmed sequence of neuron and glial cell production from isolated murine cortical stem cells. Neuron, 28, 69–80. doi:10.1016/S0896-6273(00)00086-6.

    Article  PubMed  CAS  Google Scholar 

  • Riddle, R., & Pollock, J. D. (2003). Making connections: The development of mesencephalic dopaminergic neurons. Brain Research. Developmental Brain Research, 147, 3–21. doi:10.1016/j.devbrainres.2003.09.010.

    Article  PubMed  CAS  Google Scholar 

  • Roussa, E., & Krieglstein, K. (2004). Induction and specification of midbrain dopaminergic cells: focus on SHH, FGF8, and TGF-beta. Cell and Tissue Research, 318, 23–33. doi:10.1007/s00441-004-0916-4.

    Article  PubMed  CAS  Google Scholar 

  • Roussa, E., Wiehle, M., Dunker, N., Becker-Katins, S., Oehlke, O., & Krieglstein, K. (2006). Transforming growth factor beta is required for differentiation of mouse mesencephalic progenitors into dopaminergic neurons in vitro and in vivo: Ectopic induction in dorsal mesencephalon. Stem Cells (Dayton, Ohio), 24, 2120–2129. doi:10.1634/stemcells.2005-0514.

    Article  CAS  Google Scholar 

  • Rowitch, D. H., Echelard, Y., Danielian, P. S., Gellner, K., Brenner, S., & McMahon, A. P. (1998). Identification of an evolutionarily conserved 110 base-pair cis-acting regulatory sequence that governs Wnt-1 expression in the murine neural plate. Development, 125, 2735–2746.

    PubMed  CAS  Google Scholar 

  • Rowitch, D. H., & McMahon, A. P. (1995). Pax-2 expression in the murine neural plate precedes and encompasses the expression domains of Wnt-1 and En-1. Mechanisms of Development, 52, 3–8. doi:10.1016/0925-4773(95)00380-J.

    Article  PubMed  CAS  Google Scholar 

  • Roy, N. S., Cleren, C., Singh, S. K., Yang, L., Beal, M. F., & Goldman, S. A. (2006). Functional engraftment of human ES cell-derived dopaminergic neurons enriched by coculture with telomerase-immortalized midbrain astrocytes. Nature Medicine, 12, 1259–1268. doi:10.1038/nm1495.

    Article  PubMed  CAS  Google Scholar 

  • Sanai, N., Tramontin, A. D., Quinones-Hinojosa, A., Barbaro, N. M., Gupta, N., Kunwar, S., et al. (2004). Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature, 427, 740–744. doi:10.1038/nature02301.

    Article  PubMed  CAS  Google Scholar 

  • Seeman, P., Guan, H. C., & Van Tol, H. H. (1993). Dopamine D4 receptors elevated in schizophrenia. Nature, 365, 441–445. doi:10.1038/365441a0.

    Article  PubMed  CAS  Google Scholar 

  • Smidt, M. P., & Burbach, J. P. (2007). How to make a mesodiencephalic dopaminergic neuron. Nature Reviews. Neuroscience, 8, 21–32. doi:10.1038/nrn2039.

    Article  PubMed  CAS  Google Scholar 

  • Song, H., Stevens, C. F., & Gage, F. H. (2002). Astroglia induce neurogenesis from adult neural stem cells. Nature, 417, 39–44. doi:10.1038/417039a.

    Article  PubMed  CAS  Google Scholar 

  • Tour, E., Pillemer, G., Gruenbaum, Y., & Fainsod, A. (2002). Otx2 can activate the isthmic organizer genetic network in the Xenopus embryo. Mechanisms of Development, 110, 3–13. doi:10.1016/S0925-4773(01)00591-3.

    Article  PubMed  CAS  Google Scholar 

  • Ueki, T., Tanaka, M., Yamashita, K., Mikawa, S., Qiu, Z., & Maragakis, N. J. (2003). A novel secretory factor, neurogenesin-1, provides neurogenic environmental cues for neural stem cells in the adult hippocampus. The Journal of Neuroscience, 23, 11732–11740.

    PubMed  CAS  Google Scholar 

  • Unsicker, K., Flanders, K. C., Cissel, D. S., Lafyatis, R., & Sporn, M. B. (1991). Transforming growth factor beta isoforms in the adult rat central and peripheral nervous system. Neuroscience, 44, 613–625. doi:10.1016/0306-4522(91)90082-Y.

    Article  PubMed  CAS  Google Scholar 

  • Unsicker, K., & Strelau, J. (2000). Functions of transforming growth factor-beta isoforms in the nervous system. Cues based on localization and experimental in vitro and in vivo evidence. European Journal of Biochemistry, 267, 6972–6975. doi:10.1046/j.1432-1327.2000.01824.x.

    Article  PubMed  CAS  Google Scholar 

  • varez-Buylla, A., & Lim, D. A. (2004). For the long run: Maintaining germinal niches in the adult brain. Neuron, 41, 683–686.

    Article  Google Scholar 

  • Wagner, J., Akerud, P., Castro, D. S., Holm, P. C., Canals, J. M., Snyder, E. Y., et al. (1999). Induction of a midbrain dopaminergic phenotype in Nurr1-overexpressing neural stem cells by type 1 astrocytes. Nature Biotechnology, 17, 653–659. doi:10.1038/10862.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Basic Research Program of China (2006CB500700), the key project of the Beijing Natural Science Foundation (7021002). We thank Professor Riyi Shi from the Department of Basic Medical Sciences, Purdue University for the critical reading.

Author information

Authors and Affiliations

  1. Neuroscience Research Institute, Peking University, 38 Xueyuan Road, Beijing, 100083, People’s Republic China

    Kairong Li, Bing Xue, Yue Wang, Haomin Wang & Xiaomin Wang

  2. Key Laboratory of Neuroscience (PKU), Ministry of Education, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100083, People’s Republic China

    Kairong Li, Bing Xue, Yue Wang, Haomin Wang & Xiaomin Wang

  3. Department of Neurobiology, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100083, People’s Republic China

    Kairong Li, Bing Xue, Yue Wang, Haomin Wang & Xiaomin Wang

  4. Department of Physiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, 10 Xitoutiao, Youanmen, Beijing, 100054, People’s Republic China

    Xuan Wang & Xiaomin Wang

Authors
  1. Kairong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bing Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yue Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xuan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Haomin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaomin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaomin Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, K., Xue, B., Wang, Y. et al. Ventral Mesencephalon Astrocytes Are More Efficient Than Those of Other Regions in Inducing Dopaminergic Neurons Through Higher Expression Level of TGF-β3. J Mol Neurosci 37, 288–300 (2009). https://doi.org/10.1007/s12031-008-9146-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-008-9146-7

Keywords

Search

Navigation