Centro de Envejecimiento y Regeneración, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Neurodegener Dis. 2012;10(1-4):23-6. doi: 10.1159/000333360. Epub 2012 Jan 17.
We have recently found that Wnt-5a regulates the synaptic structure and function in hippocampal neurons. This ligand is expressed in the hippocampus, stimulates dendritic spine morphogenesis and increases glutamatergic neurotransmission. Moreover, we have also shown that Wnt-5a induces the clustering of PSD-95.
To explore the role of Wnt-5a in the formation of synaptic contacts.
Primary rat hippocampal neurons were exposed to a formylated hexapeptide (Foxy-5) derived from the sequence of Wnt-5a to study synapse formation and function.
In short-term experiments, Wnt-5a only induced the clustering of PSD-95 but had no effect on the density of presynaptic puncta, while in long-term experiments, it induced both pre- and postsynaptic protein clustering and the number of synaptic contacts, in agreement with electrophysiological studies. In long-term experiments, Foxy-5 increased miniature excitatory postsynaptic current amplitude and frequency.
Our findings indicate that Wnt-5a induces synapse formation in hippocampal neurons. In addition, we discuss recent findings indicating a neuroprotective action of Wnt-5a against Aβ neurotoxicity.
我们最近发现 Wnt-5a 调节海马神经元的突触结构和功能。这种配体在海马体中表达，刺激树突棘形态发生并增加谷氨酸能神经传递。此外，我们还表明 Wnt-5a 诱导 PSD-95 的聚集。
探讨 Wnt-5a 在突触接触形成中的作用。
原代大鼠海马神经元暴露于源自 Wnt-5a 序列的甲酰化六肽（Foxy-5），以研究突触形成和功能。
在短期实验中，Wnt-5a 仅诱导 PSD-95 的聚集，而对突触前突密度没有影响，而在长期实验中，它诱导突触前和突触后蛋白的聚集以及突触接触的数量，与电生理学研究一致。在长期实验中，Foxy-5 增加了微小兴奋性突触后电流的幅度和频率。
我们的发现表明 Wnt-5a 诱导海马神经元中的突触形成。此外，我们还讨论了最近的发现，表明 Wnt-5a 对 Aβ 神经毒性具有神经保护作用。
