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Antenatal taurine improves neuronal regeneration in fetal rats with intrauterine growth restriction by inhibiting the Rho-ROCK signal pathway

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Abstract

The Rho-ROCK signal pathway is an important mediator of inhibitory signals that blocks central nervous cell regeneration. Here, we investigated whether antenatal taurine improved neuronal regeneration in fetal rats with intrauterine growth restriction (IUGR) by inhibiting this pathway. Thirty pregnant rats were randomly divided into three groups: control, IUGR, and IUGR + antenatal taurine supplementation (taurine group). The mRNA levels of Ras homolog gene A (Rho A), Rho-associated coiled-coil forming protein kinase 2 (ROCK2), and proliferating cell nuclear antigen (PCNA) were detected using real-time quantitative PCR. RhoA, ROCK2 and PCNA-positive cells were counted using immunohistochemistry. Antenatal taurine supplementation decreased RhoA and Rock2 mRNA expression, increased PCNA mRNA expression, and significantly decreased RhoA, ROCK2-positive and increased PCNA-positive cell counts in IUGR fetal rat brain tissues (p < 0.05). Thus, antenatal taurine supplementation inhibited the expression of key Rho-ROCK signal molecules and improved IUGR fetal brain development.

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References

  • Bulley S, Shen W (2009) Taurine regulation of glutamate currents through activation of a new receptor. Invest Ophthalmol Vis Sci 50(E-Abstract):1033–D941

    Google Scholar 

  • Chesney RW, Helms RA, Christensen M, Budreau AM, Han X, Sturman JA (1998) The role of taurine in infant nutrition. Adv Exp Med Biol 442:463–476

    Article  CAS  PubMed  Google Scholar 

  • Ding J, Li QY, Wang X, Sun CH, Lu CZ, Xiao BG (2010) Fasudil protects hippocampal neurons against hypoxia-reoxygenation injury by suppressing microglial inflammatory responses in mice. J Neurochem 114:1619–1629

    Article  CAS  PubMed  Google Scholar 

  • Dubreuil CI, Winton MJ, McKerracher L (2003) Rho activation patterns after spinal cord injury and the role of activated Rho in apoptosis in the central nervous system. J Cell Biol 162:233–243

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Eleftheraddes M, Creatsas G, Nicolaides K (2006) Fetal growth restriction and postnatal development. Ann NY Acad Sci 1092:319–330

    Article  Google Scholar 

  • Frisca F, Crombie DE, Dottori M, Goldshmit Y, Pébay A (2013) Rho/ROCK pathway is essential to the expansion, differentiation, and morphological rearrangements of human neural stem/progenitor cells induced by lysophosphatidic acid. J Lipid Res 54:1192–1206

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fujimura M, Usuki F, Kawamura M, Izumo S (2011) Inhibition of the Rho/ROCK pathway prevents neuronal degeneration in vitro and in vivo following methylmercury exposure. Toxicol Appl Pharmacol 250:1–9

    Article  CAS  PubMed  Google Scholar 

  • Gisselsson L, Toresson H, Ruscher K, Wieloch T (2010) Rho kinase inhibition protects CA1 cells in organotypic hippocampal slices during in vitro ischemia. Brain Res 1316:92–100

    Article  CAS  PubMed  Google Scholar 

  • Jansson N, Pettersson J, Haafiz A, Ericsson A, Palmberg I, Tranberg M, Ganapathy V, Powell TL, Jansson T (2006) Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet. J Physiol 576:935–946

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jiang W, Xia F, Han JL, Wang J (2009) Patterns of Nogo-A, NgR, and RhoA expression in the brain tissues of rats with focal cerebral infarction. Transl Res 154:40–48

    Article  CAS  PubMed  Google Scholar 

  • Kliegman RM (2011) Intrauterine growth restriction. In: Martin RJ, Fanroff AA, Walsh MC (eds) Fanaroff and Martin’s neonatal perinatal medicine, 9th edn. Elsevier Mosby, Louis, pp 245–275

    Google Scholar 

  • Kubo T, Hata K, Yamaguchi A, Yamashita T (2007) Rho-ROCK inhibitors as emerging strategies to promote nerve regeneration. Curr Pharm Des 13:2493–2499

    Article  CAS  PubMed  Google Scholar 

  • Leitner Y, Fattal-Valevski A, Geva R, Eshel R, Toledano-Alhadef H, Rotstein MI, Bassan H, Radianu B, Bitchonsky O, Jaffa AJ, Harel S (2007) Neurodevelopmental outcome of children with intrauterine growth retardation: a longitudinal, 10-year prospective study. J Child Neurol 22:580–587

    Article  PubMed  Google Scholar 

  • Li F, Teng HY, Liu J, Wang HW, Zeng L, Zhao LF (2014) Antenatal taurine supplementation increases taurine content in intrauterine growth restricted fetal rat brain tissue. Metab Brain Dis. doi:10.1007/s11011-014-9532-5

    Google Scholar 

  • Lingor P, Teusch N, Schwarz K, Mueller R, Mack H, Bahr M, Mueller BK (2007) Inhibition of Rho kinase (ROCK) increases neurite outgrowth on chondroitin sulphate proteoglycan in vitro and axonal regeneration in the adult optic nerve in vivo. J Neurochem 103:181–189

    CAS  PubMed  Google Scholar 

  • Liu J, Liu L, Chen H (2011) Antenatal taurine supplementation for improving brain ultrastructure in fetal rats with intrauterine growth restriction. Neuroscience 181:265–270

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Liu L, Wang XF, Teng HY, Yang N (2012) Antenatal supplementation of taurine for protection of fetal rat brain with intrauterine growth restriction from injury by reducing neuronal apoptosis. Neuropediatrics 43:258–263

    Article  PubMed  Google Scholar 

  • Liu J, Liu Y, Wang XF, Chen H, Yang N (2013) Antenatal taurine supplementation improves cerebral neurogenesis in fetal rats with intrauterine growth restriction through the PKA-CREB signal pathway. Nutr Neurosci 16:282–287

    Article  PubMed  Google Scholar 

  • Merezak S, Hardikar AA, Yajnik CS, Remacle C, Reusens B (2001) Intrauterine low protein diet increases fetal β-cell sensitivity to NO and IL-1: the protective role of taurine. J Endocrinol 171:299–308

    Article  CAS  PubMed  Google Scholar 

  • Ozan G, Turkozkan N, Bircan FS, Balabanli B (2012) Effect of taurine on brain 8-hydroxydeoxyguanosine and 3-nitrotyrsine levels in endotoxemia. Inflammation 35:665–670

    Article  CAS  PubMed  Google Scholar 

  • Paxions G, Watson C (2005) The rat brain in stereotaxic coordinates, 6th edn. Academic, San Diego

    Google Scholar 

  • Penna V, Stark GB, Leibig N, Boyle V, Sakalidou M (2012) Rho-inhibition by local application of c3-toxin for enhancement of axonal sprouting in a rat end-to-side nerve repair model. Microsurgery 32:207–212

    Article  CAS  PubMed  Google Scholar 

  • Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucl Acids Res 29:e45

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Raucci F, Di Fiore MM, Pinelli C, D’Aniello B, Luongo L, Polese G, Rastogi RK (2006) Proliferative activity in the frog brain: a PCNA-immunohistochemistry analysis. J Chem Neuroanat 32:127–142

    Article  CAS  PubMed  Google Scholar 

  • Ripps H, She W (2012) Taurine: a “very essential” amino acid. Mol Vis 18:2673–2686

    CAS  PubMed Central  PubMed  Google Scholar 

  • Santora A, Neuwirth LS, L’Amoreaux WJ, Idrissi AE (2013) The effects of chronic taurine supplementation on motor learning. Adv Exp Med Biol 775:177–185

    Article  CAS  PubMed  Google Scholar 

  • Satoh S, Toshima Y, Hitomi A, Ikegaki I, Seto M, Asano T (2008) Wide therapeutic time window for Rho-kinase inhibition therapy in ischemic brain damage in a rat cerebral thrombosis model. Brain Res 1193:102–108

    Article  CAS  PubMed  Google Scholar 

  • Schmandke A, Schmandke A, Strittmatter SM (2007) ROCK and Rho: biochemistry and neuronal functions of Rho-associated protein kinases. Neuroscientist 13:454–469

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tan HB, Zhong YS, Cheng Y, Shen X (2011) Rho/ROCK pathway and neural regeneration: a potential therapeutic target for central nervous system and optic nerve damage. Int J Ophthalmol 4:652–657

    PubMed Central  PubMed  Google Scholar 

  • Verner A, Craig S, McGuire W (2007) Effect of taurine supplementation on growth and development inpreterm or low birth weight infants. Cochrane Database Syst Rev 4, CD006072

    PubMed  Google Scholar 

  • Wang GH, Jiang ZL, Fan XJ, Zhang L, Li X, Ke KF (2007) Neuroprotective effect of taurine against focal cerebral ischemia in rats possibly mediated by activation of both GABA and glycine receptors. Neuropharmacology 52:1199–1209

    Article  CAS  PubMed  Google Scholar 

  • Wu J, Kohno T, Georgiev SK, Ikoma M, Ishii H, Petrenko AB, Baba H (2008) Taurine activates glycine and gamma-aminobutyric acid A receptors in rat substantia gelatinosa neurons. Neuroreport 19:333–337

    Article  CAS  PubMed  Google Scholar 

  • Wu J, Li J, Hu H, Wu D (2012) Rho-kinase inhibitor, fasudil, prevents neuronal apoptosis via the Akt activation and PTEN inactivation in the ischemic penumbra of rat brain. Cell Mol Neurobiol 32:1187–1197

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by Natural Science Foundation of China (81170577).

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The authors report no conflicts of interest.

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Correspondence to Jing Liu.

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Liu, J., Wang, HW., Liu, F. et al. Antenatal taurine improves neuronal regeneration in fetal rats with intrauterine growth restriction by inhibiting the Rho-ROCK signal pathway. Metab Brain Dis 30, 67–73 (2015). https://doi.org/10.1007/s11011-014-9572-x

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  • DOI: https://doi.org/10.1007/s11011-014-9572-x

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