Impaired long-term potentiation in c-Jun N-terminal kinase 2-deficient mice
Impaired long-term potentiation in c-Jun N-terminal kinase 2-deficient mice
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DOI：
10.1111/j.1471-4159.2005.03037.x
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发表时间：
2005-04-01
影响因子：
4.7
通讯作者：
Xiao, ZC
中科院分区：
文献类型：
--
作者：
Chen, JT;Lu, DH;Xiao, ZC
C-jun氨基末端激酶(JNKs)被认为参与调节突触的可塑性。因此，我们利用JNK2缺陷小鼠，研究了JNK2在发育过程中对海马长时程增强(LTP)的调节中的特殊作用。野生型和JNK2(-/-)小鼠海马区神经元特异性标志物NeuN和GABA阳性神经元的形态结构和数量相似。Western印迹分析显示，JNK2在1月龄和3月龄时表达较高且稳定，而JNK1在1月龄时表达较低，在3月龄野生型小鼠中几乎检测不到。与野生型小鼠相比，JNK2突变小鼠JNK1的表达显著增加，尤其是在1月龄时。电生理学研究表明，LTP在1月龄JNK2(-/-)小鼠的CA1和CA3区均有损伤，但在成年JNK2(-/-)小鼠中未见损伤，这可能是由于突触前神经递质释放减少所致。此外，在JNK2(-/-)成年小鼠中，晚期LTP受损，但早期LTP受损，这表明JNK2在将早期LTP转化为晚期LTP过程中发挥了作用。总之，这些数据强调了JNK2在发育过程中海马区突触可塑性中的具体作用。
c-Jun N-terminal kinases (JNKs) are thought to be involved in regulating synaptic plasticity. We therefore investigated the specific role of JNK2 in modulating long-term potentiation (LTP) in hippocampus during development, using JNK2-deficient mice. The morphological structure and the numbers of both NeuN, a specific neuronal marker, and GABA-positive neurons in the hippocampal areas were similar in wild-type and Jnk2(-/-) mice. Western blot analysis revealed that JNK2 expression was higher and stable at 1 and 3 months of age, but JNK1 levels were lower at 1 month of age and almost undetectable in 3-month-old wild-type mice. In contrast to wild-type mice, there was a significant increase in JNK1 expression in JNK2 mutant mice, especially at 1 month of age. Electrophysiological studies demonstrated that LTP was impaired in both the CA1 and CA3 regions in 1-month-old, but not in adult, Jnk2(-/-) mice, probably owing to decreased presynaptic neurotransmitter release. Moreover, late-phase LTP, but not early-phase LTP, was impaired in the Jnk2(-/-) adult mice, suggesting that JNK2 plays a role in transforming early LTP to late LTP. Together, the data highlight the specific role of JNK2 in hippocampal synaptic plasticity during development.