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Is GABA excitatory or inhibitory in the developing brain?

GABA 对发育中的大脑是兴奋性的还是抑制性的？

基本信息

批准号：
11480239
负责人：
NAKAMURA Shoji
金额：
$ 9.98万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11480239/
关键词：
fetal brain superior colliculus intracellular Cl^-GABA optical recording fluorescent dye umbilical cord occlusion hypoxia CIイオン発達脳 in vivo 胎仔

项目摘要

In the superior colliculus (SC) of the fetal rat brain, changes in intracellular Cl^- following focal stimulation of the SC were examined by in vivo optical recordings with Cl^- sensitive fluorescent dye. In addition, the effect of hypoxia on changes in intracellular Cl^- induced by focal SC stimulation was also examined in fetal rats which were connected with the dams by the umbilical cord. Pregnant rats were anesthetized with urethane (1.3g/kg, i.p.), the uterus was exposed by cesarean section, and partially cut to exposure of the fetus. The fetal head was attached to a stereotaxic apparatus with dental cement, and the surface of the SC was exposed. Stimulating electrodes were implanted in the rostral part of the SC.Cl^- sensitive dye was applied to the surface of the SC for optical recording of intracellular Cl^-. Fetal asphyxia was brought about by occluding the umbilical cord with a fine clip, while the recovery of the umbilical blood flow was attained by local application of papa … More verine, a relaxant of blood vessels, to the occlusion site.Focal SC stimulation increased intracellular Cl^-. This response was found to extend caudally to the entire SC from the stimulating site. In a total of 25 fetuses examined, 16 revealed Cl^- influx, 1 Cl^- efflux, and 2 both Cl^- influx and efflux following focal SC stimulation. The remaining 6 showed no change in intracellular Cl^-. Furthermore, a total of 12 fetuses were examined to assess the effect on the SC stimulation induced changes in intracellular Cl^- of hypoxia induced by umbilical cord occlusion. Before umbilical cord occlusion, 8 fetuses showed Cl^- influx following focal SC stimulation. However, 3 hours after the occlusion, the number of fetuses showing Cl^- influx was only one, and 10 fetuses revealed both Cl^- influx and efflux. The changes in intracellular Cl^- were attenuated by application of the GABA antagonist bicuculline in all cases (n=5) before umbilical cord occlusion and in 2 of 8 cases after the occlusion. These results suggest that following hypoxia Cl^- influx induced by focal SC stimulation is converted to Cl^- efflux. In addition, the changes in intracellular Cl^- are thought to occur via GABA receptors. Less

在胎鼠脑的上丘(SC)中，通过使用Cl^-敏感荧光染料进行体内光学记录来检查SC的局部刺激后细胞内Cl^-的变化。此外，还在通过脐带与母鼠连接的胎鼠中检查了缺氧对局灶性SC刺激引起的细胞内Cl^-变化的影响。妊娠大鼠用乌拉坦（1.3g/kg，腹腔注射）麻醉，剖腹产暴露子宫，部分切开暴露胎儿。用牙科水泥将胎头固定在立体定位仪上，暴露 SC 表面。将刺激电极植入 SC 的吻端部分。将 Cl^- 敏感染料应用于 SC 的表面，用于细胞内 Cl^- 的光学记录。通过用细夹夹闭脐带造成胎儿窒息，而通过在闭塞部位局部涂抹血管松弛剂papa … More verine来恢复脐带血流。局灶性SC刺激增加细胞内Cl^-。发现这种反应从刺激部位向尾部延伸到整个 SC。在总共检查的 25 个胎儿中，16 个显示 Cl^- 流入，1 个显示 Cl^- 流出，2 个在局部 SC 刺激后显示 Cl^- 流入和流出。其余6个细胞内Cl^-没有变化。此外，总共检查了12个胎儿，以评估脐带闭塞引起的缺氧对SC刺激引起的细胞内Cl^-变化的影响。脐带阻断前，8 个胎儿在局灶性 SC 刺激后出现 Cl^- 流入。然而，闭塞后3小时，显示Cl^-内流的胎儿仅1个，10个胎儿同时显示Cl^-内流和外流。在脐带闭塞前的所有病例（n=5）和脐带闭塞后的 8 例病例中的 2 例中，通过应用 GABA 拮抗剂荷包牡丹碱，细胞内 Cl^- 的变化得到减弱。这些结果表明，缺氧后，局部 SC 刺激诱导的 Cl^- 流入转化为 Cl^- 流出。此外，细胞内 Cl^- 的变化被认为是通过 GABA 受体发生的。较少的