Takeda Atsushi, Ando Masaki, Kanno Shingo, Oku Naoto
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Global COE-21, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Neurotoxicology. 2009 Jul;30(4):712-7. doi: 10.1016/j.neuro.2009.05.009. Epub 2009 Jun 6.
Extracellular zinc in the hippocampus is decreased by novelty stress. The significance of zinc movement in acute stress is unknown. In the present study, response of extracellular zinc in the hippocampus was examined after exposure to tail suspension, a behavioral stress. In rats subjected to hippocampal perfusion, thirty-second tail suspension elicited a short increase in extracellular glutamate and a persistent decrease in extracellular zinc, which continued for 60 min. These results suggest that zinc influx into hippocampal cells is facilitated by acute behavioral stress. Furthermore, the influence of the facilitated zinc influx in mossy fiber long-term potentiation (LTP) was evaluated in hippocampal slices prepared from rats 1h after tail suspension. Mossy fiber LTP was significantly attenuated. Perfusion with 100 microM ZnCl(2) prior to LTP induction was performed to facilitate zinc influx. The zinc perfusion also attenuated mossy fiber LTP. On the other hand, perfusion with 50 microM glutamate did not attenuate it. The attenuation of mossy fiber LTP by tail suspension was completely restored when rats were pretreated with clioquinol (30 mg/kg) to block the action of chelatable zinc. The present study indicates that exposure to tail suspension attenuates subsequent mossy fiber LTP. It is likely that the facilitated zinc influx by tail suspension, which seems to be linked to glutamate signaling, is involved in attenuation of subsequent mossy fiber LTP.
新奇应激会降低海马体中的细胞外锌含量。急性应激时锌移动的意义尚不清楚。在本研究中，在暴露于行为应激——悬尾实验后，检测了海马体中细胞外锌的反应。在接受海马体灌注的大鼠中，30秒的悬尾实验引起细胞外谷氨酸短暂增加，细胞外锌持续减少，并持续60分钟。这些结果表明，急性行为应激促进了锌流入海马体细胞。此外，在悬尾实验1小时后从大鼠制备的海马体切片中，评估了锌流入增加对苔藓纤维长时程增强（LTP）的影响。苔藓纤维LTP显著减弱。在LTP诱导前用100微摩尔/升氯化锌灌注以促进锌流入。锌灌注也减弱了苔藓纤维LTP。另一方面，用50微摩尔/升谷氨酸灌注并没有减弱它。当用氯碘羟喹（30毫克/千克）预处理大鼠以阻断可螯合锌的作用时，悬尾实验对苔藓纤维LTP的减弱作用完全恢复。本研究表明，暴露于悬尾实验会减弱随后的苔藓纤维LTP。悬尾实验促进的锌流入似乎与谷氨酸信号传导有关，可能参与了随后苔藓纤维LTP的减弱。
