| Co-Investigator(Kenkyū-buntansha) |
KIYAMA Hiroshi Osaka City University Graduate School of Medicine, Medical School, Professor, 医学部, 教授 (00192021)
MORITA Mitsuhiro School of Life Science, Tokyo University of Pharmacy and Life Science, Research Associate, 生命科学部, 助手 (50297602)
|
|---|
| Research Abstract |
To explore the variability in the calcium response of astrocytes to neurotransmitters, we examined factors affecting the pattern of calcium response in cultured cells and investigated the consequences of the astrocyte calcium response in slice preparations. Growth factors (epidermal growth factor plus basic fibroblast growth factor) promoted calcium oscillation in response to glutamate, ATP, or thimerosal (which directly activates the inositol-1, 4, 5 trisphosphate receptor), enlargement of the calcium store, and the development of a hypertrophic morphology, all of which were mediated by the mitogen-activated protein kinase (MAPK) cascade. All three effects were suppressed by proinflammatory cytokines (interleukin-1b or tumor necrosis factor-a), lipopolysaccharide, or a MAPK inhibitor, U0126 suggesting dual regulation of calcium oscillation in astrocytes by factors affecting brain function and pathology. In slice preparations, a metabotropic glutamate receptor agonist induced a similar calcium oscillation in neurons which was independent of synaptic transmission, indicating that the calcium response in astrocytes affects the activity of neighboring neurons as a feedback mechanism of neuronal activity.
|
