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Psychological stress-induced expression of endogenous substances with regulatory activity against GABA_A receptors and their role under pathophysiological state.

心理应激诱导的GABA_A受体调节活性内源性物质的表达及其在病理生理状态下的作用。

基本信息

批准号：
08672504
负责人：
MATSUMOTO Kinzo
金额：
$ 1.6万
依托单位：
TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

1. The data obtained in this reseach suggested that social isolation stress-induced decrease in pentobarbital (PB) sleep in mice is mediated partly by : i) an increase in neurosteroids (NS) such as pregnenolone sulfate with suppressive action on GABA_A receptors or ii) a decrease in NS such as allopregnanolone and allotetrahydrodeoxycorticosterone with facilitatory action on GABA_A receptors, or iii) both.2. In addition to neurosteroids with modulatory activity against GABA_A receptors, it was found that endogenous benzodiazepine (BZD) receptor ligands with an inverse BZD agonist property are also involved in social isolation stress-induced decrease in PB sleep in mace.3. Majonoside-R2, a major saponin component of Vietnamese ginseng with anti-stress activity, reversed the decrease in PB sleep caused by social isolation stress. This effect was antagonized by pregnenolone sulfate, suggesting that neurosteroids are involved in the anti-stress action of majonoside-R2.4.Gene expression of diazepam binding inhibitor (DBI), a putative endogenous ligand for benzodiazepine receptors in the brain, was investigated using in situ hybridization and RT-PCR techniques. Consistent with previous reports, DBI mRNA was densely expressed in the third ventricle area and hypothalamus. RT-PCR experiments revealed that social isolation stress caused the dicrease in DBI mRNA expression in the hypothalamus but not in other brain areas.These findings suggest that indection and/or increase of endogenous substances such as DBI and neurosteroids play important role in long-term socio-psychological stress-induced pathophysiology of brain funbtion.

1. 本研究获得的数据表明，社会隔离压力引起的小鼠戊巴比妥 (PB) 睡眠减少部分是由以下因素介导的：i) 神经类固醇 (NS) 的增加，例如对 GABA_A 受体具有抑制作用的孕烯醇酮硫酸盐，或 ii) NS 的减少，例如具有促进作用的别孕酮和别四氢脱氧皮质酮 GABA_A 受体，或 iii) 两者。2。除了对 GABA_A 受体具有调节活性的神经类固醇外，还发现具有反向 BZD 激动剂特性的内源性苯二氮卓 (BZD) 受体配体也参与了社交隔离应激引起的 PB 睡眠减少。 3． Majonoside-R2 是越南人参的主要皂苷成分，具有抗压力活性，可逆转社交隔离压力引起的 PB 睡眠减少。这种作用被孕烯醇酮硫酸盐拮抗，表明神经类固醇参与了majonoside-R2.4的抗应激作用。地西泮结合抑制剂（DBI）是大脑中苯二氮卓受体的假定内源性配体，使用原位杂交和RT-PCR技术研究了地西泮结合抑制剂（DBI）的基因表达。与之前的报道一致，DBI mRNA 在第三脑室区域和下丘脑中密集表达。 RT-PCR实验表明，社会隔离压力导致下丘脑DBI mRNA表达减少，但其他脑区并未出现这种情况。这些发现表明，DBI和神经类固醇等内源性物质的感染和/或增加在长期社会心理压力诱发的脑功能病理生理学中发挥着重要作用。