Bitiktaş Soner, Kandemir Başak, Tan Burak, Kavraal Şehrazat, Liman Narin, Dursun Nurcan, Dönmez-Altuntaş Hamiyet, Aksan-Kurnaz Işil, Suer Cem
aDepartment of Physiology, Faculty of Medicine bDepartment of Histology and Embryology, Faculty of Veterinary cDepartment of Medical Biology, Faculty of Medicine, Erciyes University, Kayseri dDepartment of Genetics and Bioengineering, Yeditepe University, Istanbul eMolecular Neurobiology Laboratory (AxanLab), Department of Molecular Biology and Genetics, Gebze Technical University, Kocaeli, Turkey.
Neuroreport. 2016 Aug 3;27(11):802-8. doi: 10.1097/WNR.0000000000000612.
Given evidence that mitogen-activated protein kinase (MAPK) activation is part of the nongenomic actions of thyroid hormones, we investigated the possible consequences of hyperthyroidism for the cognitive functioning of adult rats. Young adult rats were treated with L-thyroxine or saline. Twenty rats in each group were exposed to Morris water maze testing, measuring their performance in a hidden-platform spatial task. In a separate set of rats not exposed to Morris water maze testing (untrained rats), the expression and phosphorylated levels of p38-MAPK and of its two downstream effectors, Elk-1 and cAMP response element-binding protein, were evaluated using quantitative reverse transcriptase-PCR and western blotting. Rats with hyperthyroidism showed delayed acquisition of learning compared with their wild-type counterparts, as shown by increased escape latencies and distance moved on the last two trials of daily training in the water maze. The hyperthyroid rats, however, showed no difference during probe trials. Western blot analyses of the hippocampus showed that hyperthyroidism increased phosphorylated p38-MAPK levels in untrained rats. Although our study is correlative in nature and does not exclude the contribution of other molecular targets, our findings suggest that the observed impairments in acquisition during actual learning in rats with hyperthyroidism may result from the increased phosphorylation of p38-MAPK.
鉴于有证据表明丝裂原活化蛋白激酶（MAPK）激活是甲状腺激素非基因组作用的一部分，我们研究了甲状腺功能亢进对成年大鼠认知功能可能产生的影响。成年幼鼠接受L-甲状腺素或生理盐水治疗。每组20只大鼠接受莫里斯水迷宫测试，测量它们在隐藏平台空间任务中的表现。在另一组未接受莫里斯水迷宫测试的大鼠（未训练大鼠）中，使用定量逆转录聚合酶链反应和蛋白质免疫印迹法评估p38-MAPK及其两个下游效应物Elk-1和环磷酸腺苷反应元件结合蛋白的表达和磷酸化水平。与野生型大鼠相比，甲状腺功能亢进的大鼠学习获得延迟，水迷宫每日训练的最后两次试验中逃避潜伏期延长和移动距离增加就表明了这一点。然而，甲状腺功能亢进的大鼠在探索试验中没有差异。海马体的蛋白质免疫印迹分析表明，甲状腺功能亢进会增加未训练大鼠中磷酸化p38-MAPK的水平。虽然我们的研究本质上是相关性的，并未排除其他分子靶点的作用，但我们的研究结果表明甲状腺功能亢进大鼠在实际学习过程中观察到的学习障碍可能是由于p38-MAPK磷酸化增加所致。
