Antenatal Taurine Improves Intrauterine Growth-Restricted Fetal Rat Brain Development Which Is Associated with Increasing the Activity of PKA-CaMKII/c-fos Signal Pathway

Abstract

This study aimed to explore whether antenatal supplement of taurine can improve the brain development of fetal rats with intrauterine growth restriction (IUGR) via protein kinase A (PKA)-Ca²⁺/calmodulin-dependent protein kinase II (CaMKII)/c-fos pathway. A total of 30 pregnant rats were randomly divided into the following three groups: control, IUGR, and IUGR with antenatal taurine supplementation groups. The expression of PKA, CaMKII, and c-fos mRNA and proteins in fetal rat brain tissues were detected by quantitative real time (qRT)-polymerase chain reaction (PCR) and Western blot, respectively; and the number of PKA-, CaMKII- and c-fos–positive cells was measured by immunohistochemistry. Western blot and qRT-PCR revealed that antenatal taurine supplementation significantly increased PKA, CaMKII, and c-fos protein and mRNA levels in fetal rats brain with IUGR (p < 0.05). Immunohistochemistry results showed that the numbers of PKA-, CaMKII-, and c-fos–positive cells were significantly decreased in the IUGR groups compared with the controls; while antenatal taurine could significantly increase the positive cell numbers (p < 0.05). So, we conclude that antenatal taurine improves IUGR fetal brain development which is associated with increasing the activity of PKA-CaMKII/c-fos signal pathway.

Keywords

intrauterine growth restriction - taurine - protein kinase A - Ca²⁺/calmodulin-dependent protein kinase II - c-fos

• References

• 1 Liu J, Wang XF, Wang Y, Wang HW, Liu Y. The incidence rate, high-risk factors, and short- and long-term adverse outcomes of fetal growth restriction: a report from Mainland China. Medicine (Baltimore) 2014; 93 (27) e210
• 2 Chauhan SP, Beydoun H, Chang E , et al. Prenatal detection of fetal growth restriction in newborns classified as small for gestational age: correlates and risk of neonatal morbidity. Am J Perinatol 2014; 31 (3) 187-194
• 3 Chalak LF, Sikes NC, Mason MJ, Kaiser JR. Low-voltage aEEG as predictor of intracranial hemorrhage in preterm infants. Pediatr Neurol 2011; 44 (5) 364-369
• 4 Padilla N, Junqué C, Figueras F , et al. Differential vulnerability of gray matter and white matter to intrauterine growth restriction in preterm infants at 12 months corrected age. Brain Res 2014; 1545: 1-11
• 5 Simić Klarić A, Kolundžić Z, Galić S, Mejaški Bošnjak V. Language development in preschool children born after asymmetrical intrauterine growth retardation. Eur J Paediatr Neurol 2012; 16 (2) 132-137
• 6 Wang Y, Fu W, Liu J. Neurodevelopment in children with intrauterine growth restriction: adverse effects and interventions. J Matern Fetal Neonatal Med 2015; ; doi: 10.3109/14767058.2015.1015417
• 7 Jacobsson B, Ahlin K, Francis A, Hagberg G, Hagberg H, Gardosi J. Cerebral palsy and restricted growth status at birth: population-based case-control study. BJOG 2008; 115 (10) 1250-1255
• 8 Ripps H, Shen W. Review: taurine: a “very essential” amino acid. Mol Vis 2012; 18: 2673-2686
• 9 Li F, Teng HY, Liu J, Wang HW, Zeng L, Zhao LF. Antenatal taurine supplementation increases taurine content in intrauterine growth restricted fetal rat brain tissue. Metab Brain Dis 2014; 29 (3) 867-871
• 10 Liu J, Liu Y, Wang XF, Chen H, Yang N. Antenatal taurine supplementation improves cerebral neurogenesis in fetal rats with intrauterine growth restriction through the PKA-CREB signal pathway. Nutr Neurosci 2013; 16 (6) 282-287
• 11 Liu J, Wang HW, Liu F, Wang XF. Antenatal taurine improves neuronal regeneration in fetal rats with intrauterine growth restriction by inhibiting the Rho-ROCK signal pathway. Metab Brain Dis 2015; 30 (1) 67-73
• 12 Menendez-Castro C, Fahlbusch F, Cordasic N , et al. Early and late postnatal myocardial and vascular changes in a protein restriction rat model of intrauterine growth restriction. PLoS ONE 2011; 6 (5) e20369
• 13 Pepin KM, VanDalen KK, Mooers NL , et al. Quantification of heterosubtypic immunity between avian influenza subtypes H3N8 and H4N6 in multiple avian host species. J Gen Virol 2012; 93 (Pt 12) 2575-2583
• 14 El-Salhy M, Gilja OH, Gundersen D, Hausken T. Endocrine cells in the oxyntic mucosa of the stomach in patients with irritable bowel syndrome. World J Gastrointest Endosc 2014; 6 (5) 176-185
• 15 Roos S, Powell TL, Jansson T. Human placental taurine transporter in uncomplicated and IUGR pregnancies: cellular localization, protein expression, and regulation. Am J Physiol Regul Integr Comp Physiol 2004; 287 (4) R886-R893
• 16 Favretto D, Cosmi E, Ragazzi E , et al. Cord blood metabolomic profiling in intrauterine growth restriction. Anal Bioanal Chem 2012; 402 (3) 1109-1121
• 17 Bachmann VA, Bister K, Stefan E. Interplay of PKA and Rac: fine-tuning of Rac localization and signaling. Small GTPases 2013; 4 (4) 247-251
• 18 Zhou HC, Sun YY, Cai W , et al. Activation of β2-adrenoceptor enhances synaptic potentiation and behavioral memory via cAMP-PKA signaling in the medial prefrontal cortex of rats. Learn Mem 2013; 20 (5) 274-284
• 19 Lau BY, Fogerson SM, Walsh RB, Morgan JR. Cyclic AMP promotes axon regeneration, lesion repair and neuronal survival in lampreys after spinal cord injury. Exp Neurol 2013; 250: 31-42
• 20 Wang B, Zhao J, Yu M , et al. Disturbance of intracellular calcium homeostasis and CaMKII/CREB signaling is associated with learning and memory impairments induced by chronic aluminum exposure. Neurotox Res 2014; 26 (1) 52-63
• 21 Bird CW, Gardiner AS, Bolognani F , et al. KSRP modulation of GAP-43 mRNA stability restricts axonal outgrowth in embryonic hippocampal neurons. PLoS ONE 2013; 8 (11) e79255
• 22 Tu YC, Huang DY, Shiah SG, Wang JS, Lin WW. Regulation of c-Fos gene expression by NF-κB: a p65 homodimer binding site in mouse embryonic fibroblasts but not human HEK293 cells. PLoS ONE 2013; 8 (12) e84062
• 23 Gustems M, Woellmer A, Rothbauer U , et al. c-Jun/c-Fos heterodimers regulate cellular genes via a newly identified class of methylated DNA sequence motifs. Nucleic Acids Res 2014; 42 (5) 3059-3072
• 24 Tsuji M, Tanaka M, Hayashi H, Koshiishi S, Fujii K. The possible role of c-fos expression in rheumatoid joint destruction. Mod Rheumatol 2001; 11 (1) 17-22
• 25 Licata SC, Shinday NM, Huizenga MN , et al. Alterations in brain-derived neurotrophic factor in the mouse hippocampus following acute but not repeated benzodiazepine treatment. PLoS ONE 2013; 8 (12) e84806
• 26 Shen K, Teruel MN, Subramanian K, Meyer T. CaMKIIbeta functions as an F-actin targeting module that localizes CaMKIIalpha/beta heterooligomers to dendritic spines. Neuron 1998; 21 (3) 593-606
• 27 Vreugdenhil E, Datson N, Engels B , et al. Kainate-elicited seizures induce mRNA encoding a CaMK-related peptide: a putative modulator of kinase activity in rat hippocampus. J Neurobiol 1999; 39 (1) 41-50
• 28 Wang RA, Cheng G, Kolaj M, Randić M. Alpha-subunit of calcium/calmodulin-dependent protein kinase II enhances gamma-aminobutyric acid and inhibitory synaptic responses of rat neurons in vitro. J Neurophysiol 1995; 73 (5) 2099-2106
• 29 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
• 30 Liu J, Wang X, Liu Y, Yang N, Xu J, Ren X. Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction. Neural Regen Res 2013; 8 (23) 2190-2197
• 31 Liu J, Liu L, Wang XF, Teng HY, Yang N. Antenatal supplementation of taurine for protection of fetal rat brain with intrauterine growth restriction from injury by reducing neuronal apoptosis. Neuropediatrics 2012; 43 (5) 258-263
• 32 Shivaraj MC, Marcy G, Low G , et al. Taurine induces proliferation of neural stem cells and synapse development in the developing mouse brain. PLoS ONE 2012; 7 (8) e42935
• 33 Hernández-Benítez R, Ramos-Mandujano G, Pasantes-Morales H. Taurine stimulates proliferation and promotes neurogenesis of mouse adult cultured neural stem/progenitor cells. Stem Cell Res (Amst) 2012; 9 (1) 24-34
• 34 Gupta RC, Sung-Jin K. Role of taurine in organs' dysfunction and in their alleviation. Crit Care & Shock 2003; 6 (4) 191-197
• 35 Bulley S, Shen W. Reciprocal regulation between taurine and glutamate response via Ca2+-dependent pathways in retinal third-order neurons. J Biomed Sci 2010; 17 (Suppl. 01) S5
• 36 Wu JY, Wu H, Jin Y , et al. Mechanism of neuroprotective function of taurine. Adv Exp Med Biol 2009; 643: 169-179
• 37 Yao WD, Wu CF. Distinct roles of CaMKII and PKA in regulation of firing patterns and K(+) currents in Drosophila neurons. J Neurophysiol 2001; 85 (4) 1384-1394
• 38 Wasserhess P, Becker M, Staab D. Effect of taurine on synthesis of neutral and acidic sterols and fat absorption in preterm and full-term infants. Am J Clin Nutr 1993; 58 (3) 349-353
• 39 Gaull GE. Taurine in pediatric nutrition: review and update. Pediatrics 1989; 83 (3) 433-442
• 40 Wharton BA, Morley R, Isaacs EB, Cole TJ, Lucas A. Low plasma taurine and later neurodevelopment. Arch Dis Child Fetal Neonatal Ed 2004; 89 (6) F497-F498
• 41 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; 17 (4) CD006072