Downregulation of glial glutamate transporters after dopamine denervation in the striatum of 6-hydroxydopamine-lesioned rats.
Overactivity of glutamatergic neurotransmission in the basal ganglia is known to be closely related to the onset and pathogenesis of Parkinson's disease. Glutamate homeostasis around glutamatergic synapses is tightly regulated by two groups of glutamate transporters: glial glutamate transporters GLT1 (EAAT2) and GLAST (EAAT1), and neuronal glutamate transporter EAAC1. In order to investigate the changes of glutamate transporters after the onset of Parkinson's disease, unilateral 6-hydroxydopamine-lesioned rat, an animal model of Parkinson's disease, was employed. By immunofluorescence and Western blot analyses, GLT1 and GLAST proteins were significantly reduced in the striatum with lesion. No change in GLT1 and GLAST protein was found in the substantia nigra. The reduction of GLT1 protein in the striatum was more prominent than that of GLAST protein (approximately 40% vs. 20%). In addition, EAAC1 protein was found to be increased in the substantia nigra pars reticulata of the lesioned rats but not in the striatum. The present results indicate that reductions of GLT1 and GLAST may impair glutamate homeostasis around glutamatergic synapses in the striatum and contribute to over-spills of glutamate in the system. An increase in the EAAC1 level in the substantia nigra pars reticulata may increase GABA synthesis and enhance GABAergic neurotransmission. These results indicate that there are differential and distinct modulations of glutamate transporters after dopamine denervation in the 6-hydroxydopamine-lesioned rat.
Chung
E K Y
EK
Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
Chen
L W
LW
Chan
Y S
YS
Yung
K K L
KK
D018663:Adrenergic Agents / Q000633:toxicity; D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003714:Denervation; D004298:Dopamine / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D009457:Neuroglia / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018663:Adrenergic Agents; D027322:Amino Acid Transport System X-AG; D016627:Oxidopamine; D004298:Dopamine