title: Intercellular signaling pathway among Endothelia, astrocytes and neurons in excitatory neuronal damage.
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.
authors.affiliation: Medical Research Institute, Tokyo Women's Medical University, Shinjuku, Tokyo 162-8666, Japan. takakot@lab.twmu.ac.jp.
authors.forename: Takako
authors.initials: T
authors.lastname: Takemiya
authors.forename: Kanato
authors.initials: K
authors.lastname: Yamagata
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020013:Calcium Signaling; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D007608:Kainic Acid; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D000071876:Prostaglandin-E Synthases; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000378:metabolism; D015398:Signal Transduction; D009435:Synaptic Transmission
chemical_list: D018690:Excitatory Amino Acid Agonists; D058308:Receptors, Prostaglandin E, EP3 Subtype; D018698:Glutamic Acid; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone; D007608:Kainic Acid