a Jiangsu Key Laboratory of Brain Disease Bioinformation , Xuzhou Medical University , Xuzhou , Jiangsu , People's Republic of China.
b Department of Genetics , Research Center for Neurobiology Xuzhou Medical University , Xuzhou , Jiangsu , People's Republic of China.
Immunopharmacol Immunotoxicol. 2019 Feb;41(1):86-94. doi: 10.1080/08923973.2018.1549566. Epub 2019 Jan 3.
Accumulating evidence suggests that inflammation is a contributor to the cause and progression of neurodegenerative disease, such as Alzheimer's disease (AD) and Parkinson disease (PD). However, the exact mechanisms of neuroinflammation are still unclear. Here, we discussed the potential mechanisms of lipopolysaccharide (LPS)-induced brain injury via NR2B antagonists (Ro25-6981) treatment in mice. Neuroinflammation was induced in mice by virtue of LPS (1 mg/kg) by intraperitoneal injection. Immunoprecipitation was performed to measure the assembly of NR2B-calmodulin dependent protein kinase II (CaMKII)-Postsynaptic density protein 95 (PSD95) signal module in the hippocampus and frontal cortex. Nissl's staining was employed to access neuron injury in the brain. Data demonstrated that LPS could induce neuron damage, and promote the assembly of NR2B-CaMKII-PSD95 signal module and increase the expression of phosphorylated CaMKII and c-Jun N-terminal kinase (JNK) in the frontal cortex and hippocampus. However, NR2B antagonists could protect neuron injury against LPS-induced inflammation, inhibit the assembly of NR2B-CaMKII-PSD95 signal module and decrease the level of phosphorylated CaMKII and JNKs in mice. These findings indicated that the assembly of NR2B-CaMKII-PSD95 signal module is related to LPS-induced neuroinflammation, NR2B plays a key role in the assembly of NR2B-CaMKII-PSD95 signal module and NR2B antagonists could alleviate LPS-related inflammation through the reduced assembly of NR2B-CaMKII-PSD95 signal module in frontal cortex and hippocampus.
越来越多的证据表明，炎症是神经退行性疾病（如阿尔茨海默病和帕金森病）的病因和进展的一个因素。然而，神经炎症的确切机制仍不清楚。在这里，我们讨论了通过使用 NR2B 拮抗剂（Ro25-6981）治疗在小鼠中脂多糖（LPS）诱导的脑损伤的潜在机制。通过腹腔内注射 LPS（1mg/kg）在小鼠中诱导神经炎症。进行免疫沉淀以测量海马体和前额叶皮质中 NR2B-钙调蛋白依赖性蛋白激酶 II（CaMKII）-突触后密度蛋白 95（PSD95）信号模块的组装。采用尼氏染色评估大脑中的神经元损伤。数据表明，LPS 可以诱导神经元损伤，并促进 NR2B-CaMKII-PSD95 信号模块的组装，增加前额叶皮质和海马体中磷酸化 CaMKII 和 c-Jun N 端激酶（JNK）的表达。然而，NR2B 拮抗剂可以防止 LPS 诱导的炎症引起的神经元损伤，抑制 NR2B-CaMKII-PSD95 信号模块的组装，并降低小鼠中磷酸化 CaMKII 和 JNKs 的水平。这些发现表明，NR2B-CaMKII-PSD95 信号模块的组装与 LPS 诱导的神经炎症有关，NR2B 在 NR2B-CaMKII-PSD95 信号模块的组装中起关键作用，NR2B 拮抗剂可以通过减少前额叶皮质和海马体中 NR2B-CaMKII-PSD95 信号模块的组装来减轻 LPS 相关的炎症。
