Protective effect of resveratrol against nigrostriatal pathway injury in striatum via JNK pathway
Protective effect of resveratrol against nigrostriatal pathway injury in striatum via JNK pathway
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DOI：
10.1016/j.brainres.2016.10.013
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发表时间：
2017-01-01
期刊：
影响因子：
2.9
通讯作者：
Li, Hong-Peng
中科院分区：
文献类型：
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作者：
Li, Dan;Liu, Nan;Li, Hong-Peng
黑质纹状体通路损伤是一种创伤性脑损伤模型，常导致神经功能障碍或神经元坏死。最近在几种神经元变性疾病模型中证实了白藜芦醇诱导的益处。然而，白藜芦醇对神经退行性变的保护作用尚未得到明确的探索。因此，我们采用黑质纹状体通路损伤模型来模拟脑损伤。Western blot结果显示，与DMSO组相比，白藜芦醇组p-ERK蛋白表达降低，p-JNK蛋白表达增加，而p38 MAPK蛋白表达无明显变化。在损伤之前，小鼠脑室内输注白藜芦醇，有或没有JNK-IN-8，JNK 1，JNK 2和JNK 4的特异性c-JNK通路抑制剂。该研究评估了改良的神经功能评分（mNSS）和平衡木/步行试验，炎性细胞因子IL-1 β，IL-6和TNF-α的水平，以及与神经元凋亡相关的Bax和Bcl-2蛋白的纹状体表达。结果显示，白藜芦醇具有神经保护作用，如改善的mNSS和平衡木潜伏期所示，抗炎作用，如IL-1 β、TNF-α和IL-6水平降低所示。白藜芦醇还可上调p-JNK和Bcl-2蛋白表达，下调Bax蛋白表达和Fluoro-Jade C（FJC）阳性神经元数目。然而，白藜芦醇的这些优势被JNK-IN-8处理所消除。总之，我们证明白藜芦醇治疗通过激活c-JNK信号转导减弱黑质纹状体通路损伤诱导的神经元凋亡和炎症。
Nigrostriatal pathway injury is one of the traumatic brain injury models that usually lead to neurological dysfunction or neuron necrosis. Resveratrol-induced benefits have recently been demonstrated in several models of neuronal degeneration diseases. However, the protective properties of resveratrol against neurodegeneration have not been explored definitely. Thus, we employ the nigrostriatal pathway injury model to mimic the insults on the brain. Resveratrol decreased the p-ERK expression and increased the p-JNK expression compared to the DMSO group, but not alter the p38 MAPK proteins around the lesion site by Western blot. Prior to the injury, mice were infused with resveratrol intracerebroventricularly with or without JNK-IN-8, a specific c-JNK pathway inhibitor for JNK1, JNK2 and JNK4. The study assessed modified improved neurological function score (mNSS) and beam/walking test, the level of inflammatory cytokines IL-1 beta, IL-6 and TNF-alpha, and striatal expression of Bax and Bcl-2 proteins associated with neuronal apoptosis.The results revealed that resveratrol exerted a neuroprotective effect as shown by the improved mNSS and beam latency, anti-inflammatory effects as indicated by the decreased level of IL-1 beta, TNF-alpha and IL-6. Furthermore, resveratrol up-regulated the protein expression of p-JNK and Bcl-2, down-regulated the expression of Bax and the number of Fluoro-Jade C (FJC) positive neurons. However, these advantages of resveratrol were abolished by JNK-IN-8 treatment. Overall, we demonstrated that resveratrol treatment attenuates the nigrostriatal pathway injury-induced neuronal apoptosis and inflammation via activation of c-JNK signaling.