Studies on dynamic regulation of synaptic transmission by glial ATP
| Project/Area Number |
15500274
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurochemistry/Neuropharmacology
|
|---|
| Research Institution | National Institute of Health Sciences |
|---|
Principal Investigator |
KOIZUMI Schuichi Natl.Inst.Hlth.Sci., Div.Pharmacol., Lab Chief, 室長 (10280752)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | astrocytes / ATP / synapse / glia-to-neuron interaction / P2 receptor / Ca^<2+> wave / 脳血管 / グリア-ニューロン連関 / 三者間シナプス / 海馬 |
|---|
| Research Abstract |
Originally ascribed passive roles in the CNS, astrocytes are now known to have an active role in the regulation of synaptic transmission. Neuronal activity can evoke Ca^<2+> transients in astrocytes and Ca^<2+> transients in astrocytes can evoke changes in neuronal activity. The excitatory neurotransmitter glutamate has been shown to mediate such bi-directional communication between astrocytes and neurons. We demonstrate here that ATP, a primary mediator of intercellular Ca^<2+> signaling among astrocytes, also mediates intercellular signaling between astrocytes and neurons in hippocampal cultures. Mechanical stimulation of astrocytes evoked Ca^<2+> waves mediated by the release of ATP and activation of P2 receptors. Mechanically evoked Ca^<2+> waves led to decreased excitatory glutamatergic synaptic transmission in an ATP-dependent manner. Exogenous application of ATP does not affect post-synaptic glutamatergic responses but decreased pre-synaptic exocytotic events. Finally, we show that astrocytes exhibit spontaneous Ca^<2+> oscillations mediated by extracellular ATP and that inhibition of these Ca^<2+> responses enhanced excitatory glutamatergic transmission. We therefore conclude that ATP released from astrocytes exerts tonic and activity-dependent down-regulation of synaptic transmission via pre-synaptic mechanisms.
|
Report
(3 results)
Research Products
(48 results)
-
[Journal Article] Cytoprotection against oxidative-stress-induced damage of astrocytes by extra cellular ATP via P2Y1 receptors2005
Author(s)
Shinozaki, Y., Koizumi S., Ishida, S., Sawada, J., Ohno, Y., Inue, K.
-
Journal Title
Description
「研究成果報告書概要(和文)」より
Related Report
-
[Journal Article] Upregulation by retinoic acid of P2Y2 receptors in normal human epidermal keratinocytes2005
Author(s)
Inoue, K., Denda, M., Tozaki, H., Fujishita, K., Koizumi, S., Inoue, K.
-
Journal Title
J.Invest.Dermatol. 124
Pages: 756-763
Description
「研究成果報告書概要(和文)」より
Related Report
-
-
-
[Journal Article] Cytoprotection against oxidative-stress-induced damage of astrocytes by extracellular ATP via P2Y1 receptors.2005
Author(s)
Shinozaki, Y., Koizumi, S., Ishida, S., Sawada, J., Ohno, Y., Inoue, K.
-
Journal Title
Description
「研究成果報告書概要(欧文)」より
Related Report
-
[Journal Article] Characterization of multiple P2X receptors in cultured normal human epidermal keratinocytes.2005
Author(s)
Inoue, K., Denda, M., Tozaki, H., Fujishita, K., Koizumi, S., Inoue, K.
-
Journal Title
J.Invest.Dermatol. 124
Pages: 756-763
Description
「研究成果報告書概要(欧文)」より
Related Report
-
[Journal Article] Cytoprotection against oxidative-stress-induced damage of astrocytes by extracellular ATP via P2Y1 receptors2005
Author(s)
Shinozaki, Y., Koizumi S., Ishida, S., Sawada, J., Ohno, Y., Inoue, K.
-
Journal Title
Related Report
-
-
-
-
-
-
-
-
[Journal Article] Ca^<2+> waves in keratinocytes are transmitted to sensory neurons ; involvement of extracellular ATP and activation of P2Y2 receptors.2004
Author(s)
Koizumi, S., Fujishita, K., Inoue, K., Shigemoto-Mogami, Y., Tsuda, M., Inoue, K.
-
Journal Title
Biochem., J. 380
Pages: 329-338
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
[Journal Article] Activation of p38MAPK in spinal hyperactive microglia contributes to neuropathic pain hypersensitivity following peripheral nerve injury.2004
Author(s)
Tsuda, M., Mizokoshi, A., Shigemoto-Mogami, Y., Koizumi, Kohsaka, S., Inoue, K.
-
Journal Title
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Publications] Tsuda, M., Mizokoshi, A,.Shigemoto-Mogami, Y., Koizumi, S., Kohsaka, S., Inoue, K.: "Activation of p38MAPK in spinal hyperactive microglia contributes to neuropathic pain hypersensitivity following peripheral nerve injury."Glia. 45(in press). 89-95 (2004)
-
-
[Publications] Tsuda, M., Mizokoshi, A,.Shigemoto-Mogami, Y., Koizumi, S., Kohsaka, S., Salter M.W., Inoue, K.: "Induction of P2X4 ionotropic ATP receptor in spinal hyperactive microglia gates neuropathic pain."Nature. 424. 778-783 (2003)
-
-
-
-
