The BDNF Val66Met polymorphism impairs NMDA receptor-dependent synaptic plasticity in the hippocampus.
The BDNF Val66Met polymorphism impairs NMDA receptor-dependent synaptic plasticity in the hippocampus.
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DOI：
10.1523/jneurosci.1405-10.2010
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发表时间：
2010-06-30
期刊：
影响因子：
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通讯作者：
Chao MV
中科院分区：
文献类型：
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作者：
Ninan I;Bath KG;Dagar K;Perez-Castro R;Plummer MR;Lee FS;Chao MV
脑源性神经营养因子（BDNF）基因Val 66 Met多态性导致BDNF调节释放缺陷，并影响情景记忆和情感行为。然而，BDNF Val 66 Met多态性在海马突触传递和可塑性中的确切作用尚未研究。因此，我们研究了BDNFMet/Met小鼠和匹配的野生型小鼠海马CA 3-CA 1突触的突触特性。虽然基础的谷氨酸能神经传递是正常的，年轻和成年小鼠表现出显着减少N-甲基-D-天冬氨酸（NMDA）受体依赖的长时程增强。我们还发现，NMDA受体依赖的长期抑郁症在BDNFMet/Met小鼠中减少。然而，mGluR依赖的长期抑郁症不受BDNF Val 66 Met多态性的影响。与NMDA受体依赖性突触可塑性损伤一致，我们观察到BDNFMet/Met小鼠CA 1锥体神经元中NMDA受体神经传递显著减少。因此，这些结果表明，BDNF Val 66 Met多态性对NMDA受体传递有直接影响，这可能是海马突触可塑性变化的原因。
The Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene results in a defect in regulated release of BDNF and affects episodic memory and affective behaviors. However, the precise role of the BDNF Val66Met polymorphism in hippocampal synaptic transmission and plasticity has not yet been studied. Therefore, we examined synaptic properties in the hippocampal CA3-CA1 synapses of BDNFMet/Met mice and matched wild-type mice. Although basal glutamatergic neurotransmission was normal, both young and adult mice showed a significant reduction in N-methyl-D-aspartic acid (NMDA) receptor-dependent long-term potentiation. We also found that NMDA receptor-dependent long-term depression was decreased in BDNFMet/Met mice. However, mGluR-dependent long-term depression was not affected by the BDNF Val66Met polymorphism. Consistent with the NMDA receptor-dependent synaptic plasticity impairment, we observed a significant decrease in NMDA receptor neurotransmission in the CA1 pyramidal neurons of BDNFMet/Met mice. Thus, these results show that the BDNF Val66Met polymorphism has a direct effect on NMDA receptor transmission, which may account for changes in synaptic plasticity in the hippocampus.