1997 Fiscal Year Final Research Report Summary
Psychological stress-induced expression of endogenous substances with regulatory activity against GABA_A receptors and their role under pathophysiological state.
| Project/Area Number |
08672504
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
MATSUMOTO Kinzo TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY,Research Institute for Wakan-Yaku, Department of Pharmacology, Associate Professor, 和漢薬研究所, 助教授 (10114654)
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| Co-Investigator(Kenkyū-buntansha) |
TOHDA Michihisa TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY,Research Institute for Wakan-Yaku,, 和漢薬研究所, 助手 (20207525)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Social isolation stress / CNS / Neurosteroids / GABA_A receptor / Endogenous benzodiazepine receptor ligands / Pentobarbital sleep / DBI mRNA |
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| Research Abstract |
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.
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