2005 Fiscal Year Final Research Report Summary

Molecular mechanisms of anesthetics block mortility of neuronal cells

Research Project

Project/Area Number	16591548
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Anesthesiology/Resuscitation studies
Research Institution	KYUSHU UNIVERSITY
Principal Investigator	NAGATA Taro Kyushu University, Reseach Associate, 大学院・医学研究院, 助手 (70284510)
Co-Investigator(Kenkyū-buntansha)	NODA Yukiko Kyushu University, Kyushu University Hospital, Reseach Associate, 大学病院, 助手 (10404021)
Project Period (FY)	2004 – 2005
Keywords	dendritc spines / small GTPases
Research Abstract	The progress of anesthesiology has made many invasive surgical operations possible. However, little is known about the molecular mechanism of anesthetized state. We hypothesized that inhibition of actin dynamics occured during general anesthesia at brain synapses. In the present study, we investigated the influence of anesthetics on actin-based motility. NIH 3T3 cells and Swiss 3T3 cells showed actin-based ruffling at their periphery after the addition of PMA (phorbol 12-myristate 13-acetate) to the medium. Some cultures were exposed to anesthetics (propofol) before treatment of PMA, but actin rearrangement was not blocked. The same results were obtained when PDGF were added instead of PMA. We could not see the effect of anesthetics on actin rearrangement. The small GTPases Rac1 and Cdc42 are members of Rho subfamily of the Ras-related GTP-binding proteins and participates in cytoskeltal reorganization. We examined to detect the GTP-bound, active Rac/Cdc42 in neuronal cells cultured with or without the stimulation. However, active Rac/Cdc42 was difficult to detect, because of their high GTPase activity. Therefore we tried to detect Rap1 small GTPase, which also considered to be related to morphogenesis of dendritic spines. NMDA, AMPA, and their receptor antagonists did not influence Rap1 activity. It is considered that Rap1 activity is not affected by stimulation or inhibition of AMPA or NMDA receptors.