Fei F, Rao W, Zhang L, Chen B-G, Li J, Fei Z, Chen Z
Department of Cell Biology, College of Basic Medicine, Fourth Military Medical University, Xi'an 710032, PR China.
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
Neuroscience. 2014 May 16;267:187-94. doi: 10.1016/j.neuroscience.2014.02.037. Epub 2014 Mar 5.
Homer protein, a member of the post-synaptic density protein family, plays an important role in the neuronal synaptic activity and is extensively involved in neurological disorders. The present study investigates the role of Homer1b/c in modulating neuronal survival by using an in vitro traumatic neuronal injury model, which was achieved by using a punch device that consisted of 28 stainless steel blades joined together and produced 28 parallel cuts. Downregulation of Homer1b/c by specific siRNA significantly (p<0.05) alleviated the cytoplasmic calcium levels and neuron lactate dehydrogenase release, and ultimately decreased the apoptotic rate after traumatic neuronal injury compared with non-targeting siRNA control treatment in cultured rat cortical neurons. Moreover, the expression of metabotropic glutamate receptor 1a (mGluR1a) was significantly (p<0.05) reduced in the Homer1b/c siRNA-transfected neurons after injury. Therefore, Homer1b/c not only modulated the mGluR1a-inositol 1,4,5-triphosphate receptors-Ca(2+) signal transduction pathway, but also regulated the expression of mGluR1a in mechanical neuronal injury. These findings indicate that the suppression of Homer1b/c expression potentially protects neurons from glutamate excitotoxicity after injury and might be an effective intervention target in traumatic brain injury.
荷马蛋白是突触后致密蛋白家族的成员之一，在神经元突触活动中起重要作用，并广泛参与神经系统疾病。本研究通过使用体外创伤性神经元损伤模型来研究荷马1b/c在调节神经元存活中的作用，该模型是通过使用一个由28个连接在一起的不锈钢刀片组成的打孔装置实现的，该装置可产生28条平行切口。与非靶向siRNA对照处理相比，在培养的大鼠皮质神经元中，用特异性siRNA下调荷马1b/c可显著（p<0.05）减轻细胞质钙水平和神经元乳酸脱氢酶释放，并最终降低创伤性神经元损伤后的凋亡率。此外，损伤后在转染了荷马1b/c siRNA的神经元中，代谢型谷氨酸受体1a（mGluR1a）的表达显著（p<0.05）降低。因此，荷马1b/c不仅调节mGluR1a-肌醇1,4,5-三磷酸受体-Ca(2+)信号转导通路，还在机械性神经元损伤中调节mGluR1a的表达。这些发现表明，抑制荷马1b/c的表达可能保护神经元免受损伤后谷氨酸兴奋性毒性的影响，并且可能是创伤性脑损伤的一个有效干预靶点。
