title: Taurine promotes cognitive function in prenatally stressed juvenile rats via activating the Akt-CREB-PGC1α pathway.
abstract: 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.
authors: Department of Human Anatomy, Histology and Embryology, Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, PR China. Electronic address: jianing@mail.xjtu.edu.cn.
authors: Ning
authors: N
authors: Jia
authors: Institute of Forensic Medicine, Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, PR China. Electronic address: qinrusun@mail.xjtu.edu.cn.
authors: Qinru
authors: Q
authors: Sun
authors: Division of Neonatology, First Affiliated Hospital, Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, PR China.
authors: Qian
authors: Q
authors: Su
authors: Division of Neonatology, First Affiliated Hospital, Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, PR China.
authors: Shaokang
authors: S
authors: Dang
authors: Department of Human Anatomy, Histology and Embryology, Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, PR China.
authors: Guomin
authors: G
authors: Chen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000188:drug therapy* / Q000209:etiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013315:Stress, Psychological / Q000150:complications*; D013654:Taurine / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D017382:Reactive Oxygen Species; D013654:Taurine; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt-CREB-PGC1α pathway; Hippocampus; Mitochondria; Prenatal stress; Taurine