Next Article in Journal
Cholesterol Dependent Uptake and Interaction of Doxorubicin in MCF-7 Breast Cancer Cells
Next Article in Special Issue
Loss of SUMOylation on ATF3 Inhibits Proliferation of Prostate Cancer Cells by Modulating CCND1/2 Activity
Previous Article in Journal
Two Common Bean Genotypes with Contrasting Response to Phosphorus Deficiency Show Variations in the microRNA 399-Mediated PvPHO2 Regulation within the PvPHR1 Signaling Pathway
Previous Article in Special Issue
Biophysical Techniques for Detection of cAMP and cGMP in Living Cells
Int. J. Mol. Sci. 2013, 14(4), 8345-8357; doi:10.3390/ijms14048345
Review

Intercellular Signaling Pathway among Endothelia, Astrocytes and Neurons in Excitatory Neuronal Damage

1,*  and 2
1 Medical Research Institute, Tokyo Women's Medical University, Shinjuku, Tokyo 162-8666, Japan 2 Neural Plasticity Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan
* Author to whom correspondence should be addressed.
Received: 1 February 2013 / Revised: 20 March 2013 / Accepted: 3 April 2013 / Published: 16 April 2013
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
View Full-Text   |   Download PDF [5244 KB, uploaded 19 June 2014]   |   Browse Figures

Abstract

Neurons interact closely with astrocytes via glutamate; this neuron-glia circuit may play a pivotal role in synaptic transmission. On the other hand, astrocytes contact vascular endothelial cells with their end-feet. It is becoming obvious that non-neuronal cells play a critical role in regulating the neuronal activity in the brain. We find that kainic acid (KA) administration induces the expression of microsomal prostaglandin E synthase-1 (mPGES-1) in venous endothelial cells and the prostaglandin E2 (PGE2) receptor prostaglandin E receptor (EP)-3 on astrocytes. Endothelial mPGES-1 exacerbates KA-induced neuronal damage in in vivo experiments. In in vitro experiments, mPGES-1 produces PGE2, which enhances astrocytic Ca2+ levels via the EP3 receptor and increases Ca2+-dependent glutamate release, thus aggravating neuronal injury. This novel endothelium-astrocyte-neuron signaling pathway may be crucial for driving neuronal damage after repetitive seizures and could be a new therapeutic target for epilepsy and other brain disorders.
Keywords: microsomal prostaglandin E synthase-1 (mPGES-1); prostaglandin E2 (PGE2); endothelial cell; EP3; kainic acid; Ca2+ levels; astrocyte; neuronal damage microsomal prostaglandin E synthase-1 (mPGES-1); prostaglandin E2 (PGE2); endothelial cell; EP3; kainic acid; Ca2+ levels; astrocyte; neuronal damage
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share & Cite This Article

Export to BibTeX |
EndNote


MDPI and ACS Style

Takemiya, T.; Yamagata, K. Intercellular Signaling Pathway among Endothelia, Astrocytes and Neurons in Excitatory Neuronal Damage. Int. J. Mol. Sci. 2013, 14, 8345-8357.

View more citation formats

Related Articles

Article Metrics

Comments

Citing Articles

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert