Department of Psychiatry, Department of Clinical Research, University of Southern Denmark, J. B. Winsløwsvej 20, 5000, Odense, Denmark.
Psychiatry in the Region of Southern Denmark, Odense University Hospital, Odense, Denmark.
J Neural Transm (Vienna). 2019 Nov;126(11):1493-1500. doi: 10.1007/s00702-019-02073-1. Epub 2019 Sep 9.
In the present study, we developed an in vitro model of Huntington disease (HD) by transfecting primary rat hippocampal neurons with plasmids coding for m-htt exon 1 with different number of CAG repeats (18, 50 and 115) and demonstrated the influence of the length of polyQ sequence on neurite elongation. We found that exogenously applied FGF2 significantly rescued the m-htt-induced loss of neurite outgrowth. Moreover, the Enreptin peptide, an FGFR1 and NCAM dual agonist, had a similar neuritogenic effect to FGF2 in clinically relevant m-htt 50Q-expressing neurons. This study has developed an in vitro model of primary hippocampal neurons transfected with m-htt-coding vectors that is a powerful tool to study m-htt-related effects on neuronal placticity.
在本研究中，我们通过转染编码具有不同 CAG 重复数（18、50 和 115）的 m-htt 外显子 1 的质粒，建立了亨廷顿病（HD）的体外模型，并证明了多聚 Q 序列长度对神经突伸长的影响。我们发现，外源性 FGF2 可显著挽救 m-htt 诱导的神经突生长丧失。此外，Enreptin 肽是 FGFR1 和 NCAM 的双重激动剂，在具有临床相关性的 m-htt 50Q 表达神经元中，其具有类似于 FGF2 的神经突生成作用。本研究建立了一种转染 m-htt 编码载体的原代海马神经元体外模型，该模型是研究 m-htt 对神经元可塑性相关影响的有力工具。
