Regional deafferentation down-regulates subtypes of glutamate transporter proteins.
Low extracellular glutamate content is maintained primarily by high-affinity sodium-dependent glutamate transport. Three glutamate transporter proteins have been cloned: GLT-1 and GLAST are astroglial, whereas EAAC1 is neuronal. The effects of axotomy on glutamate transporter expression was evaluated in adult rats following unilateral fimbria-fornix and corticostriatal lesions. The hippocampus and striatum were collected at 3, 7, 14, and 30 days postlesion. Homogenates were immunoblotted using antibodies directed against GLT-1, GLAST, EAAC1, and glial fibrillary acidic protein and assayed for glutamate transport by D-[3H]aspartate binding. GLT-1 immunoreactivity was decreased within the ipsilateral hippocampus and striatum at 14 days postlesion. GLAST immunoreactivity was decreased within the ipsilateral hippocampus and striatum at 7 and 14 days postlesion. No alterations in EAAC1 immunoreactivity were observed. D-[3H]Aspartate binding was decreased at 14 days postlesion within the ipsilateral hippocampus and at 7 and 14 days postlesion within the ipsilateral striatum. By 30 days postlesion, glutamate transporters and D-[3H]aspartate binding returned to control levels. This study demonstrates the down-regulation of primarily glial, and not neuronal, glutamate transporters following regional disconnection.
Ginsberg
S D
SD
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Martin
L J
LJ
Rothstein
J D
JD
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000344:Afferent Pathways / Q000502:physiology; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001692:Biological Transport; D002540:Cerebral Cortex / Q000502:physiology*; D003337:Corpus Callosum / Q000502:physiology*; D003714:Denervation; D006624:Hippocampus / Q000502:physiology*; D015151:Immunoblotting; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG