Department of Neurosurgery, Shaanxi Provincial People's Hospital, Xi'an 710068, Shaanxi Province, China.
Department of Neurosurgery, Xijing Hospital, the Fourth Military Medical University of Chinese PLA, Xi'an 710032, Shaanxi Province, China.
Neural Regen Res. 2012 Oct 5;7(28):2176-81. doi: 10.3969/j.issn.1673-5374.2012.028.002.
Activation of metabotropic glutamate receptor 1a aggravates traumatic brain injury. The constitutively expressed protein Homer1b/c participates in delivering and anchoring metabotropic glutamate receptors in neurons. Here, we aimed to verify whether down-regulation of Homer1b/c by RNA interference could protect cultured rat cortical neurons from traumatic injury. We showed that 36 hours after transfection of Homer1b/c small interfering RNA, metabotropic glutamate receptor 1a was present only in the neuronal cytoplasm, but not in the dendrites. Calcium fluorescence intensity was also decreased significantly. Moreover, lactate dehydrogenase concentration was significantly decreased in Homer1b/c small interfering RNA-transfected cells compared with that in untransfected and control small interfering RNA-transfected cells 24 hours after traumatic neuronal injury. Our findings indicate that down-regulation of Homer1b/c could reduce metabotropic glutamate receptor 1a transfer from the cell body to the dendrite, relieve calcium overload, and protect neurons from traumatic injury.
代谢型谷氨酸受体 1a 的激活会加重创伤性脑损伤。组成型表达的 Homer1b/c 蛋白参与将代谢型谷氨酸受体在神经元中传递和锚定。在这里，我们旨在验证 RNA 干扰下调 Homer1b/c 是否可以保护培养的大鼠皮质神经元免受创伤损伤。结果表明，在 Homer1b/c 小干扰 RNA 转染 36 小时后，代谢型谷氨酸受体 1a 仅存在于神经元细胞质中，而不存在于树突中。钙荧光强度也显著降低。此外，与未转染和对照小干扰 RNA 转染细胞相比，创伤性神经元损伤后 24 小时，Homer1b/c 小干扰 RNA 转染细胞中的乳酸脱氢酶浓度显著降低。我们的研究结果表明，下调 Homer1b/c 可以减少代谢型谷氨酸受体 1a 从细胞体向树突的转移，减轻钙超载，并保护神经元免受创伤损伤。
