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Intercellular Signaling Pathway among Endothelia, Astrocytes and Neurons in Excitatory Neuronal Damage
Medical Research Institute, Tokyo Women's Medical University, Shinjuku, Tokyo 162-8666, Japan
Neural Plasticity Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan
* Author to whom correspondence should be addressed.
Received: 1 February 2013; in revised form: 20 March 2013 / Accepted: 3 April 2013 / Published: 16 April 2013
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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Takemiya, T.; Yamagata, K. Intercellular Signaling Pathway among Endothelia, Astrocytes and Neurons in Excitatory Neuronal Damage. Int. J. Mol. Sci. 2013, 14, 8345-8357.
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.
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.