Environmental influences on cortical development and plasticity via Cl^-homeostasis modulation

环境通过 Cl^-稳态调节对皮质发育和可塑性的影响

基本信息

批准号：
16390058
负责人：
FUKUDA Atsuo
金额：
$ 9.22万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390058/
关键词：
Cl^- transporter cortical plate cell Cajal-Retzius cell cell migration GABA taurine maternal stress Germany 国際情報交換

项目摘要

The aim of this study is to examine a validity of the hypothesis that a programmed Cl^- homeostasis of the developmental period renders GABA excitatory and promotes corticogenesis by cell migration, and that its change by environmental stimulation influence the neural circuit formation and plasticity. We established a method to distinguish between radially-migrating glutamate cells and tangentially-migrating GABA cells in living slices, by means of transfection of the HcRed gene into a GAD67-GFP knock-in mouse embryo brain in vivo. Taurine, abundantly contained in embryo brains, might act as autocrine endogenous agonist of GABA_A receptors for radial migration, and might also act as paracrine agonist for a signal to tangential migration. As for transfected ectopic KCC2, it was suggested that it did not function in vivo during radial migration. Therefore, we have designed the base sequence which was most suitable for shRNA which interfere a transcription process of a Cl^- transporter, a … More nd constructed an expression plasmid vector encoding it. Regarding the communication within the marginal zone containing the Cajal-Retzius cells which play an important role in radial migration, GABA and taurine worked as endogenous agonists of GABA_A and glycine receptors, respectively, that promoted a spread of excitation within the marginal zone. GABA_A and the glycine receptors, that were originally inhibitory, increased an excitability due to high [Cl^-]_i what was maintained by NKCC1. However, glutamate receptors which are originally excitatory did not participate. Considering maternal stress as environmental stimulation for embryos, we developed a mouse model of restriction stress to a mother, which were confined in a cylinder of 3cm diameter and 9cm in length for six hours/day from 8th to 17th gestational days. Both the body weight and the brain weight of embryos at day 18th were significantly decreased in comparison with control, indicating an influence to the embryonic brain development by maternal stress. Less

这项研究的目的是研究以下假设的有效性：发育时期的编程Cl^ - 稳态使GABA兴奋并通过细胞迁移促进皮质生成，并且其通过环境刺激的变化影响神经回路的形成和可变性。我们通过将HCRED基因翻译成Vivo中的GAD67-GFP敲击小鼠胚胎大脑的方式，建立了一种在生物切片中区分生存的谷氨酸细胞和对生物切片中切向迁移的GABA细胞的方法。牛磺酸绝对包含在胚胎大脑中，可能充当radial迁移的GABA_A受体的自分泌性内源性激动剂，并且也可能充当旁分泌激动剂，以发出与切向迁移的信号。至于转染的异位KCC2，建议它在径向迁移过程中不在体内发挥作用。因此，我们设计了最适合shRNA的碱基序列，该序列干扰了Cl^ - 转运蛋白的转录过程，A…更多地构建了编码它的表达质粒载体。关于包含Cajal-Retzius细胞的边际区域内的通信，在径向迁移中起着重要作用，GABA和牛磺酸是GABA_A和Glycine受体的内源性激动剂，从而促进了边际区域内兴奋的传播。最初是抑制性的GABA_A和甘氨酸受体，由于nkcc1所维持的，增加了令人兴奋的激动。但是，最初令人兴奋的谷氨酸受体没有参与。将物质应力作为胚胎的环境刺激，我们向母亲开发了限制应力的小鼠模型，该模型被限制在直径3厘米的圆柱体中，长度为9厘米，持续六个小时/天，从8日到17日。与对照相比，第18天胚胎的体重和脑重量都得到了显着改善，这表明物物应力对胚胎脑发育有影响。较少的