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

International Journal of Molecular Sciences

Takako Takemiya¹ 

[1]Medical Research Institute, Tokyo Women’s Medical University, Shinjuku, Tokyo 162-8666, Japan

关键词: microsomal prostaglandin E synthase-1 (mPGES-1);    prostaglandin E₂ (PGE₂);    endothelial cell;    EP3;    kainic acid;    Ca²⁺ levels;    astrocyte;    neuronal damage;   

DOI  :  10.3390/ijms14048345

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland