Synapse formation and function is modulated by the amyloid precursor protein
Synapse formation and function is modulated by the amyloid precursor protein
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DOI：
10.1523/jneurosci.1450-06.2006
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发表时间：
2006-07-05
影响因子：
5.3
通讯作者：
Herms, Jochen
中科院分区：
文献类型：
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作者：
Priller, Christina;Bauer, Thomas;Herms, Jochen
淀粉样前体蛋白(APP)在阿尔茨海默病的发病机制中起关键作用。它在神经元中的正常生物学功能仍不清楚，在神经元中，它主要位于突触。利用海马神经元的自体培养，我们证明了缺乏APP的海马神经元表现出显著增强的诱发AMPA和NMDA受体介导的EPSCs的幅度。在缺乏APP的神经元中，容易释放的突触囊泡池的大小也增加了，但释放的概率没有受到影响。此外，对自发微小突触电流的分析显示，在缺乏APP的神经元中，频率增加，而微小突触电流的幅度没有发现改变。综上所述，这些发现有力地表明，缺乏APP会增加功能性突触的数量。形态计量学免疫组织化学分析进一步支持了这一假说，显示每个培养的APP敲除神经元突触素阳性点数增加。总之，APP的缺乏影响了培养的海马神经元的突触形成和传递。
The amyloid precursor protein (APP) is critical in the pathogenesis of Alzheimer's disease. The question of its normal biological function in neurons, in which it is predominantly located at synapses, is still unclear. Using autaptic cultures of hippocampal neurons, we demonstrate that hippocampal neurons lacking APP show significantly enhanced amplitudes of evoked AMPA- and NMDA-receptor-mediated EPSCs. The size of the readily releasable synaptic vesicle pool was also increased in neurons lacking APP, whereas the release probability was not affected. In addition, the analysis of spontaneous miniature synaptic currents revealed an augmented frequency in neurons lacking APP, whereas the amplitude of miniature synaptic currents was not found to be altered. Together, these findings strongly indicate that lack of APP increases the number of functional synapses. This hypothesis is further supported by morphometric immunohistochemical analysis revealing an increase of synaptophysin-positive puncta per cultured APP knock-out neuron. In conclusion, lack of APP affects synapse formation and transmission in cultured hippocampal neurons.