کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6273972 | 1614809 | 2014 | 8 صفحه PDF | دانلود رایگان |
- Downregulation of Homer1b/c improved neuron survival after being subjected to traumatic injury.
- Downregulation of Homer1b/c altered the expression of mGluR1a.
- Downregulation of Homer1b/c attenuated overload of Ca2+ after traumatic injury.
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-Ca2+ 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.
Journal: Neuroscience - Volume 267, 16 May 2014, Pages 187-194