Expression of glutamate transporters and ionotropic glutamate receptors in GLAST knockout mice

• Published in: Brain research. Molecular brain research. Vol. 104; no. 2; pp. 120 - 126
• Main Authors: Ueda, Yuto, Doi, Taku, Tsuru, Noriko, Tokumaru, Jun, Mitsuyama, Yoshio
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.08.2002; Elsevier
• Subjects: Amino Acid Transport System X-AG - deficiency; Amino Acid Transport System X-AG - genetics; Amino Acid Transport System X-AG - metabolism; Animals; Biochemistry and metabolism; Biological and medical sciences; Central nervous system; Cortex; Down-Regulation - genetics; Epilepsy - genetics; Epilepsy - metabolism; Epilepsy - physiopathology; Excitatory Amino Acid Transporter 1; Excitatory Amino Acid Transporter 2 - metabolism; Female; Frontal Lobe - metabolism; Frontal Lobe - physiopathology; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease - genetics; Glutamate Plasma Membrane Transport Proteins; Glutamate receptor; Glutamic Acid - metabolism; Hippocampus; Hippocampus - metabolism; Hippocampus - physiopathology; Knockout; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, AMPA - metabolism; Receptors, Glutamate - metabolism; Receptors, Kainic Acid - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; Seizure; Symporters - metabolism; Synaptic Transmission - genetics; Vertebrates: nervous system and sense organs; Cortex; Glutamate receptor; Seizure; Mice; Neurotransmitters, modulators, transporters, and receptors; Knockout; Hippocampus; Ionotropic receptor; Cerebral cortex; Rodentia; Central nervous system; Gene expression; Glutamate; Vertebrata; Mammalia; Gene; Mouse; Excitatory aminoacid; Neurotransmitter; Mutation; Carrier protein; Brain (vertebrata)
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/S0169-328X(02)00325-X

In order to investigate the molecular mechanism underlying high seizure susceptibility of GLAST knockout mice, we carried out Western blotting for the expression of GLT-1, EAAC-1, and several kinds of glutamate receptors in the hippocampus and the cortex. Although no significant difference was observed between GLAST (+/+) and (−/−) mice in terms of expression of GLT-1 and EAAC-1 in the hippocampus, these proteins were over-expressed in the frontal cortex in GLAST (−/−) mice (GLT-1, about 210% increase; EAAC-1, about 180% increase). Expression of hippocampal Glu-R1 and Glu-R2 in GLAST (−/−) mice was remarkably increased (Glu-R1, about 140% increase; Glu-R2, about 160% increase), while Glu-R3 and NMDA receptors levels (NMDA-R1, 2A and 2B) were equal to those in control. Cortical levels of Glu-R1, -R2 and -R3 receptors in GLAST (−/−) mice were remarkably decreased (Glu-R1, about 60% decrease; Glu-R2, about 60% decrease; Glu-R3, about 70% decrease), while NMDA receptors were remarkably increased in comparison to those in GLAST (+/+) mice (N-R1, about 150% increase; N-R2A, about 150% increase; N-R2B, about 140% increase). These data suggest that the increased susceptibility to seizures in GLAST (−/−) mice might be derived from increased expression of Glu-R1 in the hippocampus coupled with decreased cortical expression of Glu-R2 and increased NMDA-R1 and -2A, -2B expression.