Win-Shwe Tin-Tin, Mitsushima D, Nakajima D, Ahmed S, Yamamoto S, Tsukahara S, Kakeyama M, Goto S, Fujimaki H
Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan.
Toxicol Lett. 2007 Jan 10;168(1):75-82. doi: 10.1016/j.toxlet.2006.10.017. Epub 2006 Dec 4.
Toluene, a widely used aromatic organic solvent, has been well characterized as a neurotoxic chemical. Although the neurobehavioral effects of toluene have been studied substantially, the mechanisms involved are not clearly understood. Hippocampus, which is one of the limbic areas of brain associated with neuronal plasticity, and learning and memory functions, may be a principal target of toluene. In the present study, to establish a mouse model for investigating the effects of acute toluene exposure on the amino acid neurotransmitter levels in the hippocampus, in vivo microdialysis study was performed in freely moving mice after a single intraperitoneal administration of toluene (150 and 300 mg/kg). Amino acid neurotransmitters in microdialysates were measured by a high performance liquid chromatography system. The extracellular levels of glutamate and taurine were rapidly and reversibly increased within 30 min after the toluene administration in a dose-dependent manner and returned to the basal level by 1h. Conversely, the extracellular level of glycine and GABA were stable, and no significant change was observed after the toluene administration. To further investigate the brain toluene level in the hippocampus of toluene-administered mice, we used a solid-phase microextraction (SPME) method and examined the time course changes of toluene in the hippocampus of living mice. The brain toluene level reached the peak at 30 min after injection and returned to the basal level after 2h. In the present study, we observed the relationship between brain toluene levels and amino acid neurotransmitter glutamate and taurine levels in the hippocampus. Therefore, we suggest that toluene may mediate its action through the glutamatergic and taurinergic neurotransmission in the hippocampus of freely moving mice.
甲苯是一种广泛使用的芳香族有机溶剂，已被充分确认为一种神经毒性化学物质。尽管对甲苯的神经行为效应已进行了大量研究，但其涉及的机制尚不清楚。海马体是大脑边缘系统区域之一，与神经元可塑性以及学习和记忆功能相关，可能是甲苯的主要作用靶点。在本研究中，为建立一个用于研究急性甲苯暴露对海马体中氨基酸神经递质水平影响的小鼠模型，在自由活动的小鼠单次腹腔注射甲苯（150和300毫克/千克）后进行了体内微透析研究。通过高效液相色谱系统测量微透析液中的氨基酸神经递质。甲苯给药后30分钟内，谷氨酸和牛磺酸的细胞外水平迅速且可逆地以剂量依赖方式升高，并在1小时后恢复到基础水平。相反，甘氨酸和GABA的细胞外水平稳定，甲苯给药后未观察到显著变化。为进一步研究甲苯给药小鼠海马体中的脑甲苯水平，我们使用了固相微萃取（SPME）方法，并检测了活体小鼠海马体中甲苯的时间进程变化。脑甲苯水平在注射后30分钟达到峰值，并在2小时后恢复到基础水平。在本研究中，我们观察到了脑甲苯水平与海马体中氨基酸神经递质谷氨酸和牛磺酸水平之间的关系。因此，我们认为甲苯可能通过自由活动小鼠海马体中的谷氨酸能和牛磺酸能神经传递来介导其作用。
