Toluene induces rapid and reversible rise of hippocampal glutamate and taurine neurotransmitter levels in mice.
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.
Win-Shwe
Tin-Tin
TT
Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan. tin.tin.win.shwe@nies.go.jp
Mitsushima
D
D
Nakajima
D
D
Ahmed
S
S
Yamamoto
S
S
Tsukahara
S
S
Kakeyama
M
M
Goto
S
S
Fujimaki
H
H
D000818:Animals; D005971:Glutamates / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012997:Solvents / Q000493:pharmacokinetics / Q000633:toxicity*; D013654:Taurine / Q000378:metabolism; D014050:Toluene / Q000493:pharmacokinetics / Q000633:toxicity*
D005971:Glutamates; D012997:Solvents; D013654:Taurine; D014050:Toluene