The role of NMDA receptors in neurotoxicity induced by toluene exposure during synaptogenesis

• Main Authors: Yeh-Fu Lee, 李也夫
• Other Authors: Hwei-Hsien Chen
• Format: Others
• Language: zh-TW
• Online Access: http://ndltd.ncl.edu.tw/handle/15732301725573220471

碩士 === 慈濟大學 === 藥理暨毒理學研究所 === 90 === Toluene is a wildly used industrial solvent. Human may abuse for their narcotic effects. Toluene abuse during pregnancy results in newborns with fetal solvent syndrome. Recent study indicates that toluene antagonizes the function of N-methyl-D-aspartate (NMDA) receptor. It is well known that the normal function of NMDA receptors is critical for synaptogenesis, a period when NMDA receptors are conspicuously expressed. The long-term effects of toluene exposure during synaptogenesis on the behavioral tests associated NMDA receptor function (including seizure susceptibility, locomotor activity, and pain sensitivity) and the expression of NMDA receptor subunits (NR1, NR2A and NR2B) and were examined. Sprague-Dawley rats were treated with 1000 mg/kg of toluene by intraperitoneal injection from postnatal day (PN) 4 to 9. Toluene exposure resulted in body weight reduced. There were no significant difference in day of earlap opening, eruption lower incisor, eye opening, and the ability to perform surface righting, negative geotaxis, and air righting. Toluene exposure increased latency in the hot plate test, decreased latency in tail flick test at PN 36, but decreased latency in the hot plate test at PN 67. Toluene exposure lowered NMDA-induced seizure thresholds in juveniles but not in adults. Locomotor activity was increased, but the MK-801 (0.5 mg/kg)-induced hyper-locomotor activity was reduced in the toluene-exposed rats.. The immunoblot revealed that the levels of NR2A were increased in the hippocampus and cerebellum, and levels of NR2B were decreased in the striatum and cortex in toluene-exposed rats at PN 30. The levels of NR2A were increased in the cerebellum, and levels of NR2B were decreased in the cortex in toluene-exposed rats at PN 60. Furthermore, immunohistochemistry showed that the levels of NR2A were increased in the CA1 at PN 30. There was no significant change in the levels of NR1. The results indicated that toluene exposure during synaptogenesis was associated with altered response to NMDA receptor modulator drugs and pain sensitivity, which may be related to the alteration in the expression of NMDA receptor subunits.