| Project/Area Number |
14208096
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
神経・脳内生理学
|
|---|
| Research Institution | Gunma University |
|---|
Principal Investigator |
OZAWA Seiji GUNMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学系研究科, 教授 (40049044)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TSUZUKI Keisuke GUNMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学系研究科, 助教授 (60222139)
IINO Masae GUNMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, INSTRUCTOR, 医学系研究科, 助手 (20008329)
|
|---|
| Project Period (FY) |
2002 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥50,570,000 (Direct Cost: ¥38,900,000、Indirect Cost: ¥11,670,000)
Fiscal Year 2005: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2004: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2003: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
Fiscal Year 2002: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
|
|---|
| Keywords | Glutamatergic synapse / Neuron-glia interaction / Cerebellum / Hippocampus / Glutamate transporter / GLAST / EAAT4 / AMPA receptor / GLT-1 / ベルクマングリア / プルキンエ細胞 / シナプス / Ca^<2+>透過性AMPA受容体 |
|---|
| Research Abstract |
In this study, we aimed to clarify the functional relationship between neuron and glia in glutamatergic synapses in the cerebellum and hippocampus. The main results are as follows :
1.Roles of glutamate transporters in cerebellar Purkinje cell (PC) synapses.
Four distinct glutamate transporters, GLAST, GLT-1, EAAC1 and EAAT4, are distributed near excitatory synapses in cerebellar PCs. GLAST and GLT-1 are expressed in Bergmann glia (BG) wrapping excitatory synapses on PCs, whereas EAAC1 and EAAT4 are expressed in Purkinje cells. Using mutant mice deficient in these transporter genes, we have shown that GLAST and GLT-1 contribute mainly to uptake of glutamate that floods out of the synaptic cleft at early times after transmitter release. In contrast, the main role of EAAT4 is to remove low concentrations of glutamate that escape from the uptake by glial transporters at late times and thus to prevent the transmitter from spilling over to neighboring synapses. The contribution of EAAC1 was n
… More
egligible. We have also shown that glial glutamate transporters (GLAST plus GLT-1) are expressed in surplus around PC excitatory synapses, and that only 20% of them are needed to retain the fast kinetics of EPSCs.
2.Roles of glial glutamate transporters in hippocampal pyramidal cell synapses.
Using a novel glutamate transporter blocker (TFB-TBOA) that specifically suppresses glial glutamate transporters, we have shown that the continuous uptake of synaptically released glutamate is indispensable for protecting hippocampal pyramidal neurons from NMDA receptor-mediated hyper-excitabilities. This suggests that dysfunction of glial glutamate transporters is involved in the genesis of epilepsy.
3.Regulation of the morphology of glial processes by Ca^<2+>-permeable AMPA receptors.
Using a human glioma cell line U-87 MG cells expressing AMPA receptors as a model system, we have shown that the extension of cellular processes of glial cells is regulated by manipulating expression of Ca^<2+>-permeable AMPA receptors. Less
|
