Abnormal synapse formation in agrin-depleted hippocampal neurons.

Abnormal synapse formation in agrin-depleted hippocampal neurons.
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集聚蛋白耗尽的海马神经元突触形成异常。

DOI:
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发表时间:
1999
影响因子:
4
通讯作者:
Adriana Ferreira
Adriana Ferreira
中科院分区:
生物学2区
文献类型:
--
作者:
Adriana Ferreira

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聚集蛋白是一种分子量为200 kDa的细胞外基质蛋白,参与神经肌肉接头处突触后靶点的成熟。虽然在中枢神经元中也检测到聚集蛋白,但对其在突触形成中的作用知之甚少。本研究分析了聚集蛋白在海马神经元发育过程中的表达、定位和功能。结果表明,在培养的海马神经元中,聚集蛋白水平的增加先于突触发生。聚集蛋白表达的这种增加伴随着其沿轴突远端三分之沿着的细胞外沉积。为了研究聚集蛋白是否在突触形成过程中起作用,通过反义寡核苷酸处理来抑制其在培养的海马神经元中的表达。聚集蛋白表达的抑制导致树突发育受损,并且形成比未处理或感觉处理的神经元更少的突触。此外,这种突触密度的降低伴随着GABA受体聚集的选择性抑制。这些结果表明聚集蛋白可能是中枢神经元树突成熟和突触发生的重要调节因子。
Agrin, a 200 kDa extracellular matrix protein, participates in the maturation of the postsynaptic target at the neuromuscular junction. Although agrin has also been detected in central neurons, little is known about its role in the formation of their synapses. In the present study, the pattern of expression, localization and function of agrin in developing hippocampal neurons were analyzed. The results indicate that an increase in agrin protein levels precedes synaptogenesis in cultured hippocampal neurons. This increase in agrin expression is accompanied by its extracellular deposition along the distal third of the axon. To investigate whether agrin plays a role during synapse formation, its expression in cultured hippocampal neurons was suppressed by means of antisense oligonucleotide treatment. The suppression of agrin expression results in the impairment of dendritic development and the formation of fewer synapses than in non-treated or sense-treated neurons. Moreover, this decreased synaptic density is accompanied by a selective inhibition of the clustering of GABA receptors. These results lead to the conclusion that agrin may be an important regulator of the maturation of dendrites and synaptogenesis in central neurons.
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