Project/Area Number |
06670952
|
Research Category |
Grant-in-Aid for General Scientific Research (C)
|
Allocation Type | Single-year Grants |
Research Field |
Psychiatric science
|
Research Institution | CHIBA UNIVERSITY |
Principal Investigator |
IWASA Hiroto CHIBA UNIVERSITY SCHOOL OF MEDICINE,Lecturer, 医学部, 講師 (60203361)
|
Co-Investigator(Kenkyū-buntansha) |
SHIBATA Tadahiko CHIBA UNIVERSITY SCHOOL OF MEDICINE, 医学部付属病院, 医員
HASEGAWA Shuji CHIBA CITY INSTITUTE OF HEALTH AND ENVIRONMENT,Chief, 所長 (20009640)
KOSEKI Keijirou CHIBA UNIVERSITY SCHOOL OF MEDICINE,Lecturer, 医学部, 講師 (90170258)
|
Project Period (FY) |
1994 – 1995
|
Project Status |
Completed (Fiscal Year 1995)
|
Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
Keywords | G proteins / Epilepsy / Kindling / ADP-ribosylation / Nitrin Oxide / Gs / Gi / Go / mRNA / ADPリボジル化反応 / nitric oxide / 神経可塑性 |
Research Abstract |
We examined the alteration of G protein subclasses in amygdaloid kindled rats in order to clarify the basic mechanisms of epilepsy. We found that in creases in the levels of pertussis toxin-catalyzed ADP-ribosylation on to Gi and Go are in volved with the kindling-induced epileptogenesis. Additinal study revealed that persistentincrease in the levels of nitric oxide-stimulated endognous mono-ADP-ribosylation in the kidled brain. Thirdly, expression levels of mRNAs encoding G protein alpha subunits (Gs alpha, Gi1 alpha, Gi2 alpha and Go alpha) were also examined in the cerebral cortex and hipocampus in the kindled brain. Gs mRNA level in the bilateral cerebral cortex in creased significantly at 24 hours after the last generalized seizure. The expression of Gs mRNA in creased remarkably both on the stimulated side of hippocampus and on the unstimulated side of cerebral cortex at three weeks after the last seizure. The remarkable in crease in Gi2 alpha mRNA level was observed on stimulated side of cerebral cortex at 24 hours after the last generalized seizure and persisted at least three to four weeks. These results suggest that alterations of signal transduction through G proteins and dysfunction of these G proteins, especially Gs and Gi2, might reflect the trans-synaptic changes of brain function by kindling and be related to the basic mechanisms of seizure generation and acquisition of enduring epileptogenesis.
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