Brain-derived neurotrophic factor rapidly enhances phosphorylation of the postsynaptic N-methyl-D-aspartate receptor subunit 1

Brain-derived neurotrophic factor rapidly enhances phosphorylation of the postsynaptic N-methyl-D-aspartate receptor subunit 1
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DOI:
10.1073/pnas.94.15.8191
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发表时间:
1997-07-22
影响因子:
11.1
通讯作者:
Black, IB
Black, IB
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Suen, PC;Wu, K;Black, IB

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尽管神经营养因子传统上被认为是神经元生存因子,但最近的研究表明这些因子在突触可塑性中发挥作用,特别是脑源性神经营养因子(BDNF)通过trkB受体刺激和突触后磷酸化机制快速增强海马神经元的突触传递,trkB的激活也调节海马长时程增强,其中突触后N-甲基-D-天冬氨酸谷氨酸受体发挥关键作用,然而,BDNF 增加突触后反应性的最终共同途径尚不清楚。我们现在报告,BDNF 在暴露后 5 分钟内引起 N-甲基-D-天冬氨酸受体亚基 1 磷酸化的剂量依赖性增加,这种急性效应发生在含有突触前和突触后元件的海马突触神经体中,以及在孤立的海马突触后密度中,相反,神经生长因子不会引起磷酸化增强,这些结果表明肌蛋白诱导的潜在机制突触传递的增强。
Although neurotrophins have traditionally been regarded as neuronal survival factors, recent work has suggested a role for these factors in synaptic plasticity, In particular, brain-derived neurotrophic factor (BDNF) rapidly enhances synaptic transmission in hippocampal neurons through trkB receptor stimulation and postsynaptic phosphorylation mechanisms, Activation of trkB also modulates hippocampal long-term potentiation, in which postsynaptic N-methyl-D-aspartate glutamate receptors play a key role, However, the final common pathway through which BDNF increases postsynaptic responsiveness is unknown. We now report that BDNF, within 5 min of exposure, elicits a dose-dependent increase in phosphorylation of the N-methyl-D-aspartate receptor subunit 1, This acute effect occurred in hippocampal synaptoneurosomes, which contain pre- and postsynaptic elements, and in isolated hippocampal postsynaptic densities, Nerve growth factor, in contrast, caused no enhancement of phosphorylation, These results suggest a potential mechanism for trophin-induced potentiation of synaptic transmission.