title: Inhibition of tetanically sciatic stimulation-induced LTP of spinal neurons and Fos expression by disrupting glutamate transporter GLT-1.
abstract: Tetanic stimulation of the sciatic nerve produces spinal long-term potentiation (LTP) of C-fiber evoked field potentials, which is NMDA dependent and may be the substrate of inflammation- or nerve injury-produced central sensitization. Glial glutamate transporter GLT-1 has been considered as an important regulator of excitatory synaptic transmission and nociception. In the present study, we investigated the effects of GLT-1 on the spinal LTP and Fos expression induced by tetanically sciatic stimulation. Intrathecal administration of dihydrokainate (DHK), a GLT-1 selective inhibitor, partially inhibited (0.1 mM) or completely blocked (3.0 mM) the spinal LTP, which may be related to an accumulation of extracellular glutamate. Intrathecal DHK (3.0 mM) also suppressed tetanic stimulation-induced spinal Fos expression. Double immunofluorescence showed no Fos expression in glial fibrillary acidic protein (GFAP)-positive cells, and the cell DNA fragment study failed to detect a significant apoptosis of spinal neurons. These results suggest that disruption of GLT-1 may be associated with the inhibition of functional activation of spinal neurons expressing Fos, but not with glutamate excitotoxicity. In conclusion, glial GLT-1 may play an important role in tetanically sciatic stimulation-induced LTP of spinal nociceptive neurons via the regulation of extracellular levels of glutamate to an appropriate concentration.
authors.affiliation: Institute of Neurobiology, Institutes of Brain Sciences, Fudan University, 220 Han-Dan Road, Shanghai 200433, PR China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Wang
authors.forename: Yu-Qiu
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Zhi-Qi
authors.initials: ZQ
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002452:Cell Count / Q000379:methods; D053938:DNA Fragmentation / Q000502:physiology / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D005455:Fluorescent Antibody Technique / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology / Q000528:radiation effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007211:Indoles; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D009433:Neural Inhibition / Q000502:physiology* / Q000528:radiation effects; D009475:Neurons, Afferent / Q000502:physiology* / Q000528:radiation effects; D016761:Oncogene Proteins v-fos / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000502:physiology* / Q000528:radiation effects; D013116:Spinal Cord / Q000166:cytology
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D016761:Oncogene Proteins v-fos; C007293:DAPI; C020889:dihydrokainic acid; D010751:Phosphopyruvate Hydratase; D007608:Kainic Acid