title: Downregulation of glutamate transporters is associated with elevation in extracellular glutamate concentration following rat microsphere embolism.
abstract: Sodium-dependent glutamate transporters expressed in astroglial cells and neurons are essential for clearance of extracellular glutamate. In the present study, we found elevation of extracellular glutamate concentration associated with concomitant downregulation of glutamate transporters following rat microsphere embolism (ME). A marked increase in extracellular glutamate in the rat striatum was observed by microdialysis immediately after ME induction, and glutamate remained elevated at least 12h after ischemia. Concomitantly, impairment of high KCl (146 mM)-induced glutamate release was observed in the striatum 12h after ME. Consistent with the persistent increase in extracellular glutamate, expression of the glutamate transporters EAAC1 and GLT-1 significantly decreased 6h after insult without a change in GLAST levels. GLT-1 expression was restored to basal levels within 48 h, whereas EAAC1 expression remained decreased up to at least 72 h after ME. Restoration of GLT-1 was associated with increased expression of the astroglial marker GFAP, whereas markedly reduced EACC1 levels were correlated with reduced levels of the neuronal marker MAP2, likely due to loss of vulnerable neurons. Taken together, downregulation of glutamate transporters after ME is associated with dysregulation of basal glutamate concentrations and KCl-induced glutamate release in the brain.
authors: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors: Feng
authors: F
authors: Han
authors: Norifumi
authors: N
authors: Shioda
authors: Shigeki
authors: S
authors: Moriguchi
authors: Zheng-Hong
authors: ZH
authors: Qin
authors: Kohji
authors: K
authors: Fukunaga
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D020520:Brain Infarction / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D020766:Intracranial Embolism / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D017551:Microdialysis; D008863:Microspheres; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000502:physiology
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; C493398:Slc1a1 protein, rat; D018698:Glutamic Acid; D011189:Potassium Chloride