Inhibition of LPS-induced brain injury by NR2B antagonists through reducing assembly of NR2B-CaMKII-PSD95 signal module.

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

• Authors: Yuanjian Song, Xiaofang Zhao, Di Wang, Yi Zheng, Chunxiao Dai, Mengyuan Guo, Li Qin, Xiangru Wen, Xiaoyan Zhou, Zhian Liu
• Journal: Immunopharmacology and immunotoxicology (Immunopharmacol Immunotoxicol) Vol. 41 Issue 1 Pg. 86-94 (Feb 2019) ISSN: 1532-2513 [Electronic] England
• PMID: 30604645 (Publication Type: Journal Article)

Chemical References

• Disks Large Homolog 4 Protein
• Dlg4 protein, mouse
• Lipopolysaccharides
• NR2B NMDA receptor
• Phenols
• Piperidines
• Receptors, N-Methyl-D-Aspartate
• Ro 25-6981
• Calcium-Calmodulin-Dependent Protein Kinase Type 2

Topics

• Animals
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 (metabolism)
• Disks Large Homolog 4 Protein (metabolism)
• Frontal Lobe (drug effects, immunology, metabolism)
• Hippocampus (drug effects, immunology, metabolism)
• Lipopolysaccharides (toxicity)
• Male
• Mice
• Mice, Inbred Strains
• Neurons (drug effects, metabolism)
• Phenols (pharmacology)
• Piperidines (pharmacology)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)
• Signal Transduction