Fimbria-fornix transections selectively down-regulate subtypes of glutamate transporter and glutamate receptor proteins in septum and hippocampus.
The effects of CNS axotomy on glutamate transporter and glutamate receptor expression were evaluated in adult rats following unilateral fimbria-fornix transections. The septum and hippocampus were collected at 3, 7, 14, and 30 days postlesion. Homogenates were immunoblotted by using antibodies directed against glutamate transporters (GLT-1, GLAST, and EAAC1) and glutamate receptors (GluR1, GluR2/3, GluR6/7, and NMDAR1), and they were assayed for glutamate transport by D-[3H]aspartate binding. GLT-1 was decreased at 7 and 14 days postlesion within the ipsilateral septum and at 7 days postlesion in the hippocampus. GLAST was decreased within the ipsilateral septum and hippocampus at 7 and 14 days postlesion. No postlesion alterations in EAAC1 immunoreactivity were observed. D-[3H]Aspartate binding was decreased at 7, 14, and 30 days postlesion within the ipsilateral septum and 14 days postlesion in the hippocampus. GluR2/3 expression was down-regulated at 30 days postlesion within the ipsilateral septum, whereas GluR1, GluR6/7, and NMDAR1 immunoreactivity was unchanged. In addition, no alterations in glutamate receptor expression were detected within hippocampal homogenates. This study demonstrates a selective down-regulation of primarily glial, and not neuronal, glutamate transporters and a delayed, subtype-specific down-regulation of septal GluR2/3 receptor expression after regional deafferentation within the CNS.
Ginsberg
S D
SD
Neuropathology Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Rothstein
J D
JD
Price
D L
DL
Martin
L J
LJ
D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001369:Axons / Q000502:physiology; D001692:Biological Transport / Q000502:physiology; D015153:Blotting, Western; D003720:Densitometry; D015536:Down-Regulation / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry* / Q000601:surgery; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D012686:Septal Nuclei / Q000737:chemistry* / Q000601:surgery; D014316:Tritium
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D017470:Receptors, Glutamate; D014316:Tritium; D001224:Aspartic Acid