Genetic expression alteration in autism model rats created by fetal teratogen-exposure

自闭症是一种先天性神经系统疾病，其特征是社交障碍、沟通异常、活动和好奇心有限。我们最近通过将胚胎日(E) 9大鼠胚胎暴露于沙利度胺或丙戊酸中建立了自闭症模型大鼠。在出生后50天左右观察到，暴露于E9致畸物的大鼠海马血清素、额叶皮层多巴胺和高血清素血症显著增加。在本研究中，我们检测了模型大鼠中各种基因的mRNA表达，并与对照大鼠进行比较，看看这个模型大鼠的个体基因是什么。首先，我们关注5-羟色胺转运体（5-HTT）在自闭症模型大鼠中的功能，5-HTT控制神经递质5-羟色胺从细胞外空间的再摄取，并调节5-羟色胺与其受体之间相互作用的持续时间和强度。我们分析了E11，E13和E15上的E9沙利度胺暴露胚胎的mRNA表达水平。5-111T基因的相对mRNA表达量在沙利度胺暴露于E13的胚胎中降低，而在E15的胚胎中升高。接下来，我们对自闭症模型大鼠和对照组海马中提取的mRNA在P20、30、40和50进行了DNA芯片检测，比较了600多个神经相关基因的表达。我们发现了许多变化，包括多巴胺能受体表达的变化，考虑到成年自闭症模型大鼠海马多巴胺浓度的增加，这是一个有趣的现象。其他的基因表达，包括膜转运基因，生长因子，转录因子，已经被发现，未来的精确研究是必要的，以确定何时以及什么样的遗传级联负责在人类自闭症中发现的特征性社会缺陷。

Autism is a congenital neurological disorder characterized by impairment of socialization, abnormalities of communication, and limited activity and curiosity. We have recently established autism model rats by exposing embryonic day (E) 9 rat embryo to either thalidomide or valproic acid. Significant increase of hippocampal serotonin, frontal cortex dopamine, and hyperserotonemia was observed in the E9 teratogen-exposed rats when observed around postnatal day 50. In the present study, we have examined mRNA expression of various genes in the model rats and compared with control rats, to see what is the ontogene of this model rats.First we focused on the function of serotonin transporter (5-HTT) in the autism model rat 5-HTT controls reuptake of a neurotransmitter serotonin from the extracellular space, and regulates the duration and strength of the interactions between serotonin and its receptors. We have analyzed the mRNA expression level in the E9 thalidomide exposed embryos on E11,E13, and E15. Relative mRNA expression of 5-111T gene was decreased in the thalidomide exposed embryos on E13, but increased on E15, compared to the controls. Next we performed DNA microarray of mRNA extracted from hippocampus of autism model rats and controls on P20, 30, 40 and 50, and compared over 600 neuro-related gene expression. Many changes were found including change in dopaminergic receptor expression, which is intriguing when considering increase of dopamine concentration in the hippocampus of adult autism model rats. Other genetic expression, including membrane trafficking genes, growth factors, transcription factors, were found, and future precise investigation is necessary to determine when and what genetic cascade is responsible for the characteristic social defect found in autism in humans.