Involvement of NMDA receptor subunits in zinc-mediated modification of CA1 LTP in the developing hippocampus
Involvement of NMDA receptor subunits in zinc-mediated modification of CA1 LTP in the developing hippocampus
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NMDA 受体亚基参与发育中海马 CA1 LTP 锌介导的修饰
DOI：
10.1002/jnr.22787
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
et al
中科院分区：
文献类型：
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作者：
Atsushi Takeda;et al
锌是一种内源性 N-甲基-D-天冬氨酸 (NMDA) 受体阻滞剂。锌介导的海马 CA1 长时程增强 (LTP) 修饰可能与 NMDA 受体亚基的表达有关，而 NMDA 受体亚基的表达随出生后发育而变化。在本研究中，在未成熟（3 周龄）和年轻（6 周龄）大鼠的海马切片中检查了 ZnCl2 和 CaEDTA（一种膜不可渗透的锌螯合剂）对 CA1 LTP 诱导的影响。破伤风（10-100 Hz，1 秒）诱导的 CA1 LTP 在 3 周龄大鼠中显着增强。在 3 周龄大鼠中，CA1 LTP 在 2-氨基-5-磷酸戊酸 (APV)（一种 NMDA 受体拮抗剂）和 CaEDTA 存在下受到抑制，与之前报道的 6 周龄大鼠的情况一样。另一方面，在 3 周龄大鼠中，5 μM ZnCl2 比 6 周龄大鼠更能减弱 NMDA 受体介导的 EPSP，并显着减弱 CA1 LTP。此外，在 3 周龄大鼠中，在 (2R,4S)-4-(3-膦酰基丙基)-2-哌啶甲酸 (PPPA)（一种 NR2A 拮抗剂）存在下，5 μM ZnCl2 显着减弱 CA1 LTP，但在存在艾芬地尔（一种 NR2B 拮抗剂）时则不然，这表明锌介导的 CA1 LTP 减弱与 NR2B 的优先表达相关。 3周龄大鼠的亚单位。然而，在 6 周大的大鼠中，5 μM ZnCl2 显着增强了 CA1 LTP，并且在 PPPA 存在的情况下也显着增强了 CA1 LTP。本研究表明内源性锌可能参与 CA1 LTP 的诱导。 NMDA 受体亚基表达的变化可能与发育中海马中 CA1 LTP 的锌介导修饰有关。 © 2011 Wiley 期刊公司。
Zinc is an endogenous N‐methyl‐D‐aspartate (NMDA) receptor blocker. It is possible that zinc‐mediated modification of hippocampal CA1 long‐term potentiation (LTP) is linked to the expression of NMDA receptor subunits, which varies with postnatal development. In the present study, the effect of ZnCl2and CaEDTA, a membrane‐impermeable zinc chelator, on CA1 LTP induction was examined in hippocampal slices from immature (3‐week‐old) and young (6‐week‐old) rats. Tetanus (10–100 Hz, 1 sec)‐induced CA1 LTP was more greatly enhanced in 3‐week‐old rats. CA1 LTP was inhibited in the presence of 2‐amino‐5‐phosphonovalerate (APV), an NMDA receptor antagonist, and CaEDTA in 3‐week‐old rats, as in the case of 6‐week‐old rats reported previously. In 3‐week‐old rats, on the other hand, 5 μM ZnCl2attenuated NMDA receptor‐mediated EPSPs more than in 6‐week‐old rats and significantly attenuated CA1 LTP. Moreover, 5 μM ZnCl2significantly attenuated CA1 LTP in the presence of (2R,4S)‐4‐(3‐phosphonopropyl)‐2‐piperidinecarboxylic acid (PPPA), an NR2A antagonist, in 3‐week‐old rats, but not that in the presence of ifenprodil, an NR2B antagonist, suggesting that zinc‐mediated attenuation of CA1 LTP is associated with the preferential expression of NR2B subunit in 3‐week‐old rats. In 6‐week‐old rats, however, 5 μM ZnCl2significantly potentiated CA1 LTP and also CA1 LTP in the presence of PPPA. The present study demonstrates that endogenous zinc may participate in the induction of CA1 LTP. It is likely that the changes in expression of NMDA receptor subunits are involved in the zinc‐mediated modification of CA1 LTP in the developing hippocampus. © 2011 Wiley Periodicals, Inc.