Jia Ning, Sun Qinru, Su Qian, Dang Shaokang, Chen Guomin
Department of Human Anatomy, Histology and Embryology, Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, PR China.
Institute of Forensic Medicine, Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, PR China.
Redox Biol. 2016 Dec;10:179-190. doi: 10.1016/j.redox.2016.10.004. Epub 2016 Oct 13.
Substantial evidence has shown that the oxidative damage to hippocampal neurons is associated with the cognitive impairment induced by adverse stimuli during gestation named prenatal stress (PS). Taurine, a conditionally essential amino acid, possesses multiple roles in the brain as a neuromodulator or antioxidant. In this study, to explore the roles of taurine in PS-induced learning and memory impairment, prenatal restraint stress was set up and Morris water maze (MWM) was employed for testing the cognitive function in the one-month-old rat offspring. The mitochondrial reactive oxygen species (ROS) level，mitochondrial membrane potential (MMP), ATP and cytochrome c oxidase (CcO) activity and apoptosis-related proteins in the hippocampus were detected. The activity of the Akt-cyclic AMP response element-binding protein (CREB)-peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) pathway in the hippocampus was measured. The results showed that high dosage of taurine administration in the early postnatal period attenuated impairment of spatial learning and memory induced by PS. Meanwhile, taurine administration diminished the increase in mitochondrial ROS, and recovered the reduction of MMP, ATP level and the activities of CcO, superoxide dismutase 2 (SOD2) and catalase induced by PS in the hippocampus. In addition, taurine administration recovered PS-suppressed SOD2 expression level. Taurine administration blocked PS-induced decrease in the ratio of Bcl-2/Bax and increase in the ratio of cleaved caspase-3/full-length caspase-3. Notably, taurine inhibited PS-decreased phosphorylation of Akt (pAkt) and phosphorylation of CREB (pCREB), which consequently enhanced the mRNA and protein levels of PGC1α. Taken together, these results suggest that high dosage of taurine administration during the early postnatal period can significantly improve the cognitive function in prenatally stressed juvenile rats via activating the Akt-CREB-PGC1α pathway. Therefore, taurine has therapeutic potential for prenatal stressed offspring rats in future.
大量证据表明，海马神经元的氧化损伤与孕期不良刺激（称为产前应激，PS）诱导的认知障碍有关。牛磺酸是一种条件必需氨基酸，在大脑中作为神经调节剂或抗氧化剂发挥多种作用。在本研究中，为了探讨牛磺酸在PS诱导的学习和记忆损伤中的作用，建立了产前束缚应激模型，并采用莫里斯水迷宫（MWM）测试1月龄大鼠后代的认知功能。检测了海马中线粒体活性氧（ROS）水平、线粒体膜电位（MMP）、ATP和细胞色素c氧化酶（CcO）活性以及凋亡相关蛋白。测定了海马中Akt-环磷酸腺苷反应元件结合蛋白（CREB）-过氧化物酶体增殖物激活受体γ共激活因子1α（PGC1α）通路的活性。结果表明，出生后早期给予高剂量牛磺酸可减轻PS诱导的空间学习和记忆损伤。同时，牛磺酸给药减少了线粒体ROS的增加，并恢复了PS诱导的海马中MMP、ATP水平以及CcO、超氧化物歧化酶2（SOD2）和过氧化氢酶活性的降低。此外，牛磺酸给药恢复了PS抑制的SOD2表达水平。牛磺酸给药阻止了PS诱导的Bcl-2/Bax比值降低和裂解的半胱天冬酶-3/全长半胱天冬酶-3比值增加。值得注意的是，牛磺酸抑制了PS降低的Akt（pAkt）磷酸化和CREB（pCREB）磷酸化，从而提高了PGC1α的mRNA和蛋白水平。综上所述这些结果表明，出生后早期给予高剂量牛磺酸可通过激活Akt-CREB-PGC1α通路显著改善产前应激幼鼠的认知功能。因此，牛磺酸对未来产前应激的后代大鼠具有治疗潜力。
