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,* email and 2email
Received: 1 February 2013; in revised form: 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)
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.
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
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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.

AMA Style

Takemiya T, Yamagata K. Intercellular Signaling Pathway among Endothelia, Astrocytes and Neurons in Excitatory Neuronal Damage. International Journal of Molecular Sciences. 2013; 14(4):8345-8357.

Chicago/Turabian Style

Takemiya, Takako; Yamagata, Kanato. 2013. "Intercellular Signaling Pathway among Endothelia, Astrocytes and Neurons in Excitatory Neuronal Damage." Int. J. Mol. Sci. 14, no. 4: 8345-8357.


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