Molecular functional evaluation of brain/spinal GABA receptor subunit in response to excitation of signal transduction

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12671504
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Tokyo Medical University
• Principal Investigator: ITO Hitoyuki Tokyo Medical University, Medicine, Instructor, 医学部, 助手 (20317837)
• Co-Investigator(Kenkyū-buntansha): WATANABE Yasuo Tokyo Medical University Medicinem, Ass Prof, 医学部, 助教授 (70183720)
• Project Period (FY): 2000 – 2001
• Keywords: GABA a receptor / α4 subinit / vobtile anesthetics / anesthesia / brain ishemia / brain protection / C57BL / 6J

Research Abstract

By the recent research of molecular biology, the subunit of GABA receptor has been clearly analyzed and the several subclass of GABAa receptor has been evaluated. In this study, the functional role of α4 subunit of GABAa receptor on the anesthesia condition of intravenous(I.v.) anesthetic and the neuronal death induced by brain ischemia was investigated As an experimental animal, C57Bl/6J mouse which has an incomplete Willis arterial circle and shows the dissimilar pharrnacological potency to each I.v. anesthetics was used in this experiments. (1)After two dosages administrations of each I.v.anesthetic to C57BL/6J mice, I.e., midazolam, pentobarbital and propofol, the anesthesia condition was classfied into two groups, such as a complete, which means full loss of the righting reflex, and an incomplete which means half loss of the righting reflex, anesthesia conditions. In case of a complete anesthesia condition, the expression of α4 subunit of GABAa receptor mNA in the several brain regions induced by propofol was significantly higher than that induced by other I.v. anesthetics and volatile anestetic. In case of an incomplete anesthesia condition, however, α4 subunit mNA expression induced by midazolam and pentobarbital, but not propofol, was significantly higher than that seen in those complete anesthesia conditions. These results suggest that α4 subunit of GABAa receptor is more sensitive to propofol, not midazolam and pentobarbital. (2)Twenty-four hours after brain ischemia, more than 60% of brain regions were significantly damaged. However, the rich regions of α4 subunit mNA expression after brain ischemia did not show the severe damages. Thus the functional role of brain α4 subunit of GABAa receptor relates to the neuronal protections.