Antenatal Supplementation of Taurine for Protection of Fetal Rat Brain with Intrauterine Growth Restriction from Injury by Reducing Neuronal Apoptosis

Abstract

This study aimed to investigate whether antenatal taurine can reduce neuronal apoptosis in fetal rat brains with intrauterine growth restriction (IUGR) and its possible mechanisms. A total of 15 pregnant rats were randomly divided into the following three groups: control, IUGR, and IUGR+ antenatal taurine supplements. Neuronal apoptosis was detected using transferase-mediated dUTP biotin nick end-labeling (TUNEL); the expression of Bcl-2, Bax, and caspase-3 mRNA and proteins was detected by reverse transcription-polymerase chain reaction and immunohistochemistry. In IUGR groups, the results were as follows: (1) the expression of Bcl-2 decreased whereas the expression of Bax increased, accordingly, the ratio of Bcl-2/Bax decreased, (2) the expression of caspase-3 increased significantly, and (3) apoptotic neuron counts in IUGR groups was significantly increased compared with controls. In taurine supplement groups, the results were as follows: (1) the expression of Bcl-2 increased whereas the expression of Bax decreased, accordingly, the ratio of Bcl-2/Bax increased, (2) the expression of caspase-3 in fetal rat cerebral cortex tissues decreased significantly, and (3) the number of apoptotic neurons was significantly decreased compared with IUGR groups. In addition, the changes in the expression of Bcl-2, Bax, and caspase-3 mRNA and protein were correlated. So we concluded that antenatal supplementation of taurine may reduce neuronal apoptosis in IUGR fetal rats via up-regulating the ratio of Bcl-2/Bax and down-regulating the expression of caspase-3.

Keywords

intrauterine growth restriction - taurine - neuronal - cerebrum - apoptosis - the ratio of Bcl-2/Bax - caspase-3

• References

• 1 Romo A, Carceller R, Tobajas J. Intrauterine growth retardation (IUGR): epidemiology and etiology. Pediatr Endocrinol Rev 2009; 6 (Suppl. 03) 332-336
• 2 Walid MS, Astafyeva OV, Pomortsev AV. The IUGR prognostic scale. Arch Gynecol Obstet 2007; 276 (6) 633-640
• 3 Richards M, Hardy R, Kuh D, Wadsworth ME. Birth weight and cognitive function in the British 1946 birth cohort: longitudinal population based study. BMJ 2001; 322 (7280) 199-203
• 4 Strauss RS. Adult functional outcome of those born small for gestational age: twenty-six-year follow-up of the 1970 British Birth Cohort. JAMA 2000; 283 (5) 625-632
• 5 Samuelsen GB, Pakkenberg B, Bogdanović N , et al. Severe cell reduction in the future brain cortex in human growth-restricted fetuses and infants. Am J Obstet Gynecol 2007; 197 (1) 56 , e1–e7
• 6 Tolsa CB, Zimine S, Warfield SK , et al. Early alteration of structural and functional brain development in premature infants born with intrauterine growth restriction. Pediatr Res 2004; 56 (1) 132-138
• 7 Morley R, Fewtrell MS, Abbott RA, Stephenson T, MacFadyen U, Lucas A. Neurodevelopment in children born small for gestational age: a randomized trial of nutrient-enriched versus standard formula and comparison with a reference breastfed group. Pediatrics 2004; 113 (3 Pt 1) 515-521
• 8 Chesney RW, Helms RA, Christensen M, Budreau AM, Han X, Sturman JA. The role of taurine in infant nutrition. Adv Exp Med Biol 1998; 442: 463-476
• 9 Liu J, Liu L, Chen H. Antenatal taurine supplementation for improving brain ultrastructure in fetal rats with intrauterine growth restriction. Neuroscience 2011; 181: 265-270
• 10 Breckenridge DG, Xue D. Regulation of mitochondrial membrane permeabilization by BCL-2 family proteins and caspases. Curr Opin Cell Biol 2004; 16 (6) 647-652
• 11 Ola MS, Nawaz M, Ahsan H. Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem 2011; 351 (1–2) 41-58
• 12 Jansson N, Pettersson J, Haafiz A , et al. Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet. J Physiol 2006; 576 (Pt 3) 935-946
• 13 Merezak S, Hardikar AA, Yajnik CS, Remacle C, Reusens B. Intrauterine low protein diet increases fetal beta cell sensitivity to NO and IL1 beta: the protective role of taurine. J Endocrinol 2001; 171 (2) 299-308
• 14 Chen H, Liu J. Effects of intrauterine growth limitation on perinatal brain development. Zhonghua Er Ke Za Zhi 2009; 47 (1) 33-35
• 15 Junyent F, Romero R, de Lemos L , et al. Taurine treatment inhibits CaMKII activity and modulates the presence of calbindin D28k, calretinin, and parvalbumin in the brain. J Neurosci Res 2010; 88 (1) 136-142
• 16 Saransaari P, Oja SS. Modulation of taurine release in ischemia by glutamate receptors in mouse brain stem slices. Amino Acids 2010; 38 (3) 739-746
• 17 Albamonte MS, Willis MA, Albamonte MI, Jensen F, Espinosa MB, Vitullo AD. The developing human ovary: immunohistochemical analysis of germ-cell-specific VASA protein, BCL-2/BAX expression balance and apoptosis. Hum Reprod 2008; 23 (8) 1895-1901
• 18 Sun M, Xu C. Neuroprotective mechanism of taurine due to up-regulating calpastatin and down-regulating calpain and caspase-3 during focal cerebral ischemia. Cell Mol Neurobiol 2008; 28 (4) 593-611
• 19 Taranukhin AG, Taranukhina EY, Saransaari P, Djatchkova IM, Pelto-Huikko M, Oja SS. Taurine reduces caspase-8 and caspase-9 expression induced by ischemia in the mouse hypothalamic nuclei. Amino Acids 2008; 34 (1) 169-174
• 20 Bulley S, Shen W. Taurine regulation of glutamate currents through activation of a new receptor. Invest Ophthalmol Vis Sci 2009; 50: 1033-D941
• 21 Wang GH, Jiang ZL, Fan XJ, Zhang L, Li X, Ke KF. Neuroprotective effect of taurine against focal cerebral ischemia in rats possibly mediated by activation of both GABAA and glycine receptors. Neuropharmacology 2007; 52 (5) 1199-1209
• 22 Verner A, Craig S, McGuire W. Effect of taurine supplementation on growth and development in preterm or low birth weight infants. Cochrane Database Syst Rev 2007; (4) CD006072
• 23 Taranukhin AG, Taranukhina EY, Saransaari P, Podkletnova IM, Pelto-Huikko M, Oja SS. Neuroprotection by taurine in ethanol-induced apoptosis in the developing cerebellum. J Biomed Sci 2010; 17 (Suppl. 01) S12