Taurine 9 pp 457-472 | Cite as

Taurine Enhances Proliferation and Promotes Neuronal Specification of Murine and Human Neural Stem/Progenitor Cells

Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 803)


Brain development is impaired in taurine deficient animals, showing neuronal delayed maturation and migration. To get insight in the mechanism of this requirement, our studies examined the effect of taurine deficiency in stem/progenitor cells (collectively named neural precursor cells, NPCs). NPCs obtained from mesencephalon of mice embryos (E13.5 days), the subventricular zone of adult mice or human fetal brain, were cultured in media containing EGF and bFGF, and grown as neurospheres. NPCs become taurine-deficient after few days in culture. Addition of taurine replenished the cell pool by a taurine transporter, functionally expressed in NPCs. Taurine-containing cultures contain higher number of cells, due to increased proliferation, evaluated by BrdU incorporation and flow cytometry DNA analysis. Taurine effects are not immediate, requiring a long time interaction with cells. Taurine is not present in cell nuclei, discarding a direct action on nuclear elements. Taurine containing cultures show a higher number of cells with more efficient mitochondrial potential, as detected by flow cytometry assays using rhodamine123/NAO and JC1. A microarray analysis revealed that taurine regulates NPC genes implicated in proliferation, survival, adhesion and mitochondrial functioning. NPCs cultured in medium with bovine fetal serum differentiate into astrocytes, neurons and oligodendrocytes. A markedly high number of neurons were found in taurine cultures from NPCs from adult murine brain (229 %) and human fetal brain (307 %). This effect may also be a consequence of a better mitochondrial functioning as neuronal survival in cultures is markedly affected by the energy state of the cell during the differentiation phase.


Neurogenesis Neural precursor cells Stem cell proliferation Neurosphere cultures DNA microarray Mitochondrial function 





Basic fibroblast growth factor


Carboxyfluorescein diacetate succinimidyl ester


Database for annotation, visualization and integrated discovery


Epidermal growth factor


Glial fibrillary acidic protein


5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethylbenzimi-dazolylcarbocyanine iodide


Kyoto encyclopedia of genes and genomes


Lewis X


Microtubule-associated protein 2


Myelin basic protein


Mitochondrial transfer Ribonucleic acid


3-(4,5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide


10-N-nonyl acridine orange


Neural precursor cells


Paired box protein 6


Sonic Hedgehog


Subventricular zone


Taurine transporter







This work was supported by the grant PAPIIT-IN202313 from the Dirección General de Asuntos del Personal Académico (DGAPA).


  1. Agrawal HC, Davis JM, Himwich WA (1968) Maturational changes in amino acids in CNS of different mammalian species. Recent Adv Biol Psychiatry 10:258–265CrossRefPubMedGoogle Scholar
  2. Aguirre GD (1978) Retinal degeneration associated with the feeding of dog foods to cats. J Am Vet Med Assoc 172(7):791–796PubMedGoogle Scholar
  3. Ahmed S (2009) The culture of neural stem cells. J Cell Biochem 106(1):1–6CrossRefPubMedGoogle Scholar
  4. Bankson DD, Russell RM (1988) Protein energy malnutrition and taurine supplementation: effects on vitamin A nutritional status and electroretinogram of young rats. J Nutr 118(1):23–32PubMedGoogle Scholar
  5. Canu N, Barbato C, Ciotti MT, Serafino A, Dus L, Calissano P (2000) Proteasome involvement and accumulation of ubiquitinated proteins in cerebellar granule neurons undergoing apoptosis. J Neurosci 20(2):589–599PubMedGoogle Scholar
  6. Chen XC, Pan ZL, Liu DS, Han X (1998) Effect of taurine on human fetal neuron cells: proliferation and differentiation. Adv Exp Med Biol 442:397–403CrossRefPubMedGoogle Scholar
  7. Froger N, Cadetti L, Lorach H, Martins J, Bemelmans AP, Dubus E, Degardin J, Pain D, Forster V, Chicaud L, Ivkovic I, Simonutti M, Fouquet S, Jammoul F, Leveillard T, Benosman R, Sahel JA, Picaud S (2012) Taurine provides neuroprotection against retinal ganglion cell degeneration. PLoS One 7(10):e42017CrossRefPubMedCentralPubMedGoogle Scholar
  8. Geggel H, Heckenlively J, Martin D, Ament M, Kopple J (1982) Human retinal dysfunction and taurine deficiency. Doc Ophthal Proc Ser 31:199–207, G. N. a. C. Huber. Los Angeles, California, Dr. W. Junk Publishers, The HagueGoogle Scholar
  9. Gondo Y, Satsu H, Ishimoto Y, Iwamoto T, Shimizu M (2012) Effect of taurine on mRNA expression of thioredoxin interacting protein in Caco-2 cells. Biochem Biophys Res Commun 426(3):433–437CrossRefPubMedGoogle Scholar
  10. Han X, Chesney RW (2013) Knockdown of TauT expression impairs human embryonic kidney 293 cell development. Adv Exp Med Biol 776:307–320CrossRefPubMedGoogle Scholar
  11. Hayes KC, Carey RE, Schmidt SY (1975) Retinal degeneration associated with taurine deficiency in the cat. Science 188(4191):949–951CrossRefPubMedGoogle Scholar
  12. Hernandez-Benitez R, Pasantes-Morales H, Pinzon-Estrada E, Ramos-Mandujano G (2010a) Functional expression and subcellular localization of the taurine transporter TauT in murine neural precursors. Dev Neurosci 32(4):321–328CrossRefPubMedGoogle Scholar
  13. Hernandez-Benitez R, Pasantes-Morales H, Saldana IT, Ramos-Mandujano G (2010b) Taurine stimulates proliferation of mice embryonic cultured neural progenitor cells. J Neurosci Res 88(8):1673–1681PubMedGoogle Scholar
  14. 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(1):24–34CrossRefPubMedGoogle Scholar
  15. 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(1):40–49CrossRefPubMedGoogle Scholar
  16. Liang J, Deng X, Wu FS, Tang YF (2013) Transcriptomic and proteomic analysis of human hepatic stellate cells treated with natural taurine. Mol Med Rep 7(5):1442–1452PubMedGoogle Scholar
  17. 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
  18. Liu J, Wang HW, Liu F, Wang XF (2014) Antenatal taurine improves neuronal regeneration in fetal rats with intrauterine growth restriction by inhibiting the Rho-ROCK signal pathway. Metab Brain Dis 30(1):67–73Google Scholar
  19. 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(5):491–502CrossRefPubMedGoogle Scholar
  20. 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(1):45–56CrossRefPubMedGoogle Scholar
  21. Mortensen OH, Olsen HL, Frandsen L, Nielsen PE, Nielsen FC, Grunnet N, Quistorff B (2010a) Gestational protein restriction in mice has pronounced effects on gene expression in newborn offspring’s liver and skeletal muscle; protective effect of taurine. Pediatr Res 67(1):47–53CrossRefPubMedGoogle Scholar
  22. Mortensen OH, Olsen HL, Frandsen L, Nielsen PE, Nielsen FC, Grunnet N, Quistorff B (2010b) A maternal low protein diet has pronounced effects on mitochondrial gene expression in offspring liver and skeletal muscle; protective effect of taurine. J Biomed Sci 17(Suppl 1):S38CrossRefPubMedCentralPubMedGoogle Scholar
  23. Neuringer M, Denny D, Sturman J (1979) Reduced plasma taurine concentration and core electroretinogram amplitude in monkeys fed a protein-deficient semipurified diet. J Nutr 109(6 Suppl):26Google Scholar
  24. 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
  25. Ostrakhovitch EA, Semenikhin OA (2012) The role of redox environment in neurogenic development. Arch Biochem Biophys 534(1–2):44–54PubMedGoogle Scholar
  26. Palackal T, Moretz R, Wisniewski H, Sturman J (1986) Abnormal visual cortex development in the kitten associated with maternal dietary taurine deprivation. J Neurosci Res 15(2):223–239CrossRefPubMedGoogle Scholar
  27. Palackal T, Sturman J, Moretz R, Wisniewski H (1985) Feline maternal taurine deficiency: abnormal ontogeny of visual cortex. Trans Am Soc Neurochem 16:186Google Scholar
  28. Park SH, Lee H, Park KK, Kim HW, Park T (2006) Taurine-responsive genes related to signal transduction as identified by cDNA microarray analyses of HepG2 cells. J Med Food 9(1):33–41CrossRefPubMedGoogle Scholar
  29. Pasantes-Morales H, Hernandez-Benitez R (2010) Taurine and brain development: trophic or cytoprotective actions? Neurochem Res 35(12):1939–1943CrossRefPubMedGoogle Scholar
  30. Ramasamy S, Narayanan G, Sankaran S, Yu YH, Ahmed S (2013) Neural stem cell survival factors. Arch Biochem Biophys 534(1–2):71–87CrossRefPubMedGoogle Scholar
  31. Ramos-Mandujano G, Hernandez-Benitez R, Pasantes-Morales H (2014) Multiple mechanisms mediate the taurine-induced proliferation of neural stem/progenitor cells from the subventricular zone of the adult mouse. Stem Cell Res 12(3):690–702CrossRefPubMedGoogle Scholar
  32. Reynolds BA, Tetzlaff W, Weiss S (1992) A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. J Neurosci 12(11):4565–4574PubMedGoogle Scholar
  33. Ricketts JD (1983) Feline central retinal degeneration in the domestic cat. J Small Anim Pract 24(4):221–227CrossRefGoogle Scholar
  34. Rietze RL, Reynolds BA (2006) Neural stem cell isolation and characterization. Methods Enzymol 419:3–23CrossRefPubMedGoogle Scholar
  35. Shivaraj MC, Marcy G, Low G, Ryu JR, Zhao X, Rosales FJ, Goh EL (2012) Taurine induces proliferation of neural stem cells and synapse development in the developing mouse brain. PLoS One 7(8):e42935CrossRefPubMedCentralPubMedGoogle Scholar
  36. Smith DE, Downs I (1978) Postnatal development of the granule cell in the kitten cerebellum. Am J Anat 151(4):527–537CrossRefPubMedGoogle Scholar
  37. Sturman JA, Gaull GE (1975) Taurine in the brain and liver of the developing human and monkey. J Neurochem 25(6):831–835CrossRefPubMedGoogle Scholar
  38. 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(3):405–416CrossRefPubMedGoogle Scholar
  39. Sturman JA, Palackal T, Imaki H, Moretz RC, French J, Wisniewski HM (1987) Nutritional taurine deficiency and feline pregnancy and outcome. Adv Exp Med Biol 217:113–124CrossRefPubMedGoogle Scholar
  40. Sturman JA, Wen GY, Wisniewski HM, Neuringer MD (1984) Retinal degeneration in primates raised on a synthetic human infant formula. Int J Dev Neurosci 2(2):121–129CrossRefPubMedGoogle Scholar
  41. Sturman JA, Wen GY, Wisniewski HM, Niemann WH, Hayes KC (1981) Taurine and tapetum structure. Adv Exp Med Biol 139:65–78CrossRefPubMedGoogle Scholar
  42. Suzuki T, Miyauchi K, Yokobori S, Shigi N, Kondow A, Takeuchi N, Yamagishi A, Watanabe K (2011) Taurine-containing uridine modifications in tRNA anticodons are required to decipher non-universal genetic codes in ascidian mitochondria. J Biol Chem 286(41):35494–35498CrossRefPubMedCentralPubMedGoogle Scholar
  43. Suzuki T, Wada T, Saigo K, Watanabe K (2002) Taurine as a constituent of mitochondrial tRNAs: new insights into the functions of taurine and human mitochondrial diseases. EMBO J 21(23):6581–6589CrossRefPubMedCentralPubMedGoogle Scholar
  44. Tappaz ML (2004) Taurine biosynthetic enzymes and taurine transporter: molecular identification and regulations. Neurochem Res 29(1):83–96CrossRefPubMedGoogle Scholar
  45. Vucic D, Dixit VM, Wertz IE (2011) Ubiquitylation in apoptosis: a post-translational modification at the edge of life and death. Nat Rev Mol Cell Biol 12(7):439–452CrossRefPubMedGoogle Scholar
  46. Warskulat U, Andree B, Lusebrink J, Kohrer K, Haussinger D (2006) Switch from actin alpha1 to alpha2 expression and upregulation of biomarkers for pressure overload and cardiac hypertrophy in taurine-deficient mouse heart. Biol Chem 387(10–11):1449–1454PubMedGoogle Scholar
  47. Wen GY, Sturman JA, Wisniewski HM, Lidsky AA, Cornwell AC, Hayes KC (1979) Tapetum disorganization in taurine-depleted cats. Invest Ophthalmol Vis Sci 18(11):1200–1206PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.División de Neurociencias, Instituto de Fisiología CelularUniversidad Nacional Autónoma de MéxicoMexico CityMexico

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