Altered expressions of glutamate transporter subtypes in rat model of neonatal cerebral hypoxia-ischemia.
Glutamate transporters are essential for maintaining the extracellular levels of glutamate at synaptic clefts and are regulated developmentally in a subtype-specific manner. We investigated chronological changes of immunoreactivities for glial glutamate transporters GLAST and GLT-1 and a neuronal glutamate transporter, EAAC1, in postnatal 7-day-old rat neocortices and hippocampi at 12, 24, 48 and 72 h after hypoxia-ischemia. Glutamate transporter subtypes are differentially expressed in the ischemic core and the boundary area of the neonatal rat brain with hypoxia-ischemia. Expressions of these glutamate transporters decreased in the ischemic core at 12 h, then immunoreactivities for GLAST and GLT-1 were recovered at the hippocampus. This was accompanied by a GFAP-positive gliosis at 72 h, whereas these immunoreactivities were reduced at the neocortex in the ischemic core. Glial glutamate transporters, especially GLAST, were noted in some astrocytes appearing as apoptosis as well as shrunken pyramidal neurons mainly in the boundary area of the neocortex. Increased perikaryal expression of EAAC1 was associated with that of MAP2 at the border of the boundary area. These temporal and regional expressions of glutamate transporters may contribute towards understanding the excitotoxic cell death mechanism in hypoxic-ischemic encephalopathy during the perinatal period.
Fukamachi
S
S
Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka, 812-8582, Japan.
Furuta
A
A
Ikeda
T
T
Ikenoue
T
T
Kaneoka
T
T
Rothstein
J D
JD
Iwaki
T
T
D027322:Amino Acid Transport System X-AG / Q000032:analysis / Q000096:biosynthesis*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis; D004195:Disease Models, Animal; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2 / Q000032:analysis / Q000096:biosynthesis*; D050580:Excitatory Amino Acid Transporter 3; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D005911:Gliosis / Q000378:metabolism / Q000473:pathology; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters
D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D005904:Glial Fibrillary Acidic Protein; D050491:Glutamate Plasma Membrane Transport Proteins; C493398:Slc1a1 protein, rat; C493392:Slc1a3 protein, rat; D027981:Symporters; D018698:Glutamic Acid