Neurochemical Research

, Volume 40, Issue 5, pp 924–931 | Cite as

Taurine Enhances Excitability of Mouse Cochlear Neural Stem Cells by Selectively Promoting Differentiation of Glutamatergic Neurons Over GABAergic Neurons

  • Qin Wang
  • Gang-hua Zhu
  • Ding-hua Xie
  • Wei-jing Wu
  • Peng Hu
Original Paper


Taurine is a sulfur-containing amino acid present in high concentrations in mammalian tissues, and has been implicated in several processes involving brain development and neurotransmission. However, the role of taurine in inner ear neural development is still largely unknown. Here we report that taurine enhanced the viability and proliferation of in vitro mouse cochlear neural stem cell culture, as well as improved neurite outgrowth. Moreover, prolonged taurine treatment also increased the neural electrical activity by escalating changes of intracellular calcium concentration, the number of spontaneous Ca2+ oscillations in cells, and the frequencies of Ca2+ spikes. Most importantly, we found that this escalated neural excitability by taurine was due to combined effect of increase in the population of excitatory glutamatergic neuron and decrease in inhibitory GABAergic neuron population. This is the first report on the effect of taurine to selectively promote neural stem cell differentiation by altering neuron type commitment. Our study has supported the potential of taurine as treatment against hearing loss caused by neuron degeneration, or even as an agent to improve sensitivity of hearing by increasing overall excitability of auditory nervous system.


Taurine Cochlear neural stem cell Glutamatergic neuron Differentiation 



This study was supported by Chinese Major National Science Research Program (Nos. 2012CB967900, 2012CB967904), the National Natural Science Foundation of China (No. 81100716) and the Eleventh Five-Year Plan for Deaf Children Cochlear Implantation of Hunan Province.

Conflict of interest

Authors declare no competing financial interests exist concerning the content of this document.

Supplementary material

11064_2015_1546_MOESM1_ESM.docx (2 mb)
Fig. S1 NSCs were able to differentiate into neurons (labeled by MAP-2), astrocytes (labeled by GFAP) and oligodendrocytes (labeled by O4) following either control or 10 mM taurine treatment after culturing for 2 weeks. Scale bar = 100 µm. (DOCX 2069 kb)


  1. 1.
    Chai R, Kuo B, Wang T, Liaw EJ, Xia A, Jan TA, Liu Z, Taketo MM, Oghalai JS, Nusse R, Zuo J, Cheng AG (2012) Wnt signaling induces proliferation of sensory precursors in the postnatal mouse cochlea. Proc Natl Acad Sci USA 109:8167–8172CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    Cox BC, Chai R, Lenoir A, Liu Z, Zhang L, Nguyen DH, Chalasani K, Steigelman KA, Fang J, Rubel EW, Cheng AG, Zuo J (2014) Spontaneous hair cell regeneration in the neonatal mouse cochlea in vivo. Development 141:816–829CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Li H, Liu H, Heller S (2003) Pluripotent stem cells from the adult mouse inner ear. Nat Med 9:1293–1299CrossRefPubMedGoogle Scholar
  4. 4.
    Yerukhimovich MV, Bai L, Chen DH, Miller RH, Alagramam KN (2007) Identification and characterization of mouse cochlear stem cells. Dev Neurosci 29:251–260CrossRefPubMedGoogle Scholar
  5. 5.
    Martinez-Monedero R, Yi E, Oshima K, Glowatzki E, Edge AS (2008) Differentiation of inner ear stem cells to functional sensory neurons. Dev Neurobiol 68:669–684CrossRefPubMedGoogle Scholar
  6. 6.
    Reyes JH, O’Shea KS, Wys NL, Velkey JM, Prieskorn DM, Wesolowski K, Miller JM, Altschuler RA (2008) Glutamatergic neuronal differentiation of mouse embryonic stem cells after transient expression of neurogenin 1 and treatment with BDNF and GDNF: in vitro and in vivo studies. J Neurosci 28:12622–12631CrossRefPubMedCentralPubMedGoogle Scholar
  7. 7.
    Chen Y, Dong C (2009) Aβ40 promotes neuronal cell fate in neural progenitor cells. Cell Death Differ 16:386–394CrossRefPubMedGoogle Scholar
  8. 8.
    Matsumoto M, Nakagawa T, Kojima K, Sakamoto T, Fujiyama F, Ito J (2008) Potential of embryonic stem cell-derived neurons for synapse formation with auditory hair cells. J Neurosci Res 86:3075–3085CrossRefPubMedGoogle Scholar
  9. 9.
    Sturman JA, Moretz RC, French JH, Wisniewski HM (1985) Taurine deficiency in the developing cat: persistence of the cerebellar external granule cell layer. J Neurosci Res 13:405–416CrossRefPubMedGoogle Scholar
  10. 10.
    Neuringer M, Palackal T, Kujawa M, Moretz RC, Sturman JA (1990) Visual cortex development in rhesus monkeys deprived of dietary taurine. Prog Clin Biol Res 351:415–422PubMedGoogle Scholar
  11. 11.
    Maar T, Moran J, Schousboe A, Pasantes-Morales H (1995) Taurine deficiency in dissociated mouse cerebellar cultures affects neuronal migration. Int J Dev Neurosci 13:491–502CrossRefPubMedGoogle Scholar
  12. 12.
    Nguyen TT, Bhattarai JP, Park SJ, Han SK (2013) Activation of glycine and extrasynaptic GABA(A) receptors by taurine on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis. Neural Plast 2013:740581PubMedCentralPubMedGoogle Scholar
  13. 13.
    Qian T, Chen R, Nakamura M, Furukawa T, Kumada T, Akita T, Kilb W, Luhmann HJ, Nakahara D, Fukuda A (2014) Activity-dependent endogenous taurine release facilitates excitatory neurotransmission in the neocortical marginal zone of neonatal rats. Front cell Neurosci 8:33CrossRefPubMedCentralPubMedGoogle Scholar
  14. 14.
    Horner KC, Aurousseau C (1997) Immunoreactivity for taurine in the cochlea: its abundance in supporting cells. Hear Res 109:135–142CrossRefPubMedGoogle Scholar
  15. 15.
    Oshima K, Senn P, Heller S (2009) Isolation of sphere-forming stem cells from the mouse inner ear. Methods Mol Biol 493:141–162CrossRefPubMedCentralPubMedGoogle Scholar
  16. 16.
    Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260:3440–3450PubMedGoogle Scholar
  17. 17.
    Brouhard GJ, Rice LM (2014) The contribution of αβ-tubulin curvature to microtubule dynamics. J Cell Biol 207:323–334CrossRefPubMedGoogle Scholar
  18. 18.
    Thomas AP, Bird GS, Hajnoczky G, Robb-Gaspers LD, Putney JW Jr (1996) Spatial and temporal aspects of cellular calcium signaling. FASEB J 10:1505–1517PubMedGoogle Scholar
  19. 19.
    Bjorklund U, Persson M, Ronnback L, Hansson E (2010) Primary cultures from cerebral cortex and hippocampus enriched in glutamatergic and GABAergic neurons. Neurochem Res 35:1733–1742CrossRefPubMedGoogle Scholar
  20. 20.
    Minelli A, Brecha NC, Karschin C, DeBiasi S, Conti F (1995) GAT-1, a high-affinity GABA plasma membrane transporter, is localized to neurons and astroglia in the cerebral cortex. J Neurosci 15:7734–7746PubMedGoogle Scholar
  21. 21.
    Miller TJ, Hanson RD, Yancey PH (2000) Developmental changes in organic osmolytes in prenatal and postnatal rat tissues. Comp Biochem Physiol A Mol Integr Physiol 125:45–56CrossRefPubMedGoogle Scholar
  22. 22.
    Hernandez-Benitez R, Pasantes-Morales H, Saldana IT, Ramos-Mandujano G (2010) Taurine stimulates proliferation of mice embryonic cultured neural progenitor cells. J Neurosci Res 88:1673–1681PubMedGoogle Scholar
  23. 23.
    Hernandez-Benitez R, Ramos-Mandujano G, Pasantes-Morales H (2012) Taurine stimulates proliferation and promotes neurogenesis of mouse adult cultured neural stem/progenitor cells. Stem Cell Res 9:24–34CrossRefPubMedGoogle Scholar
  24. 24.
    Hernandez-Benitez R, Vangipuram SD, Ramos-Mandujano G, Lyman WD, Pasantes-Morales H (2013) Taurine enhances the growth of neural precursors derived from fetal human brain and promotes neuronal specification. Dev Neurosci 35:40–49CrossRefPubMedGoogle Scholar
  25. 25.
    Liu J, Liu L, Chen H (2011) Antenatal taurine supplementation for improving brain ultrastructure in fetal rats with intrauterine growth restriction. Neuroscience 181:265–270CrossRefPubMedGoogle Scholar
  26. 26.
    Eagleson GW, Ubink R, Jenks BG, Roubos EW (1998) Forebrain differentiation and axonogenesis in amphibians: I. Differentiation of the suprachiasmatic nucleus in relation to background adaptation behavior. Brain Behav Evol 52:23–36CrossRefPubMedGoogle Scholar
  27. 27.
    Wilson SW, Houart C (2004) Early steps in the development of the forebrain. Dev Cell 6:167–181CrossRefPubMedCentralPubMedGoogle Scholar
  28. 28.
    Azim K, Fischer B, Hurtado-Chong A, Draganova K, Cantu C, Zemke M, Sommer L, Butt A, Raineteau O (2014) Persistent Wnt/beta-catenin signaling determines dorsalization of the postnatal subventricular zone and neural stem cell specification into oligodendrocytes and glutamatergic neurons. Stem Cells 32:1301–1312CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Qin Wang
    • 1
  • Gang-hua Zhu
    • 1
  • Ding-hua Xie
    • 1
  • Wei-jing Wu
    • 1
  • Peng Hu
    • 1
  1. 1.Department of Otolaryngology and Head & Neck Surgery, The Second Xiangya HospitalCentral South UniversityChangshaChina

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