MTEP Impedes the Neuronal Polarization and the Activity of the Akt-NF-κB Pathway in Rat Hippocampal Neurons

作者：Zhang, Xiaohua; Hu, Ming; Zhang, Lin; An, Jing; Yan, Wenhui; Zhang, Zhichao; Liu, Jianxin; Lu, Haixia; Chen, Xinlin^*; Liu, Yong^*

来源：Journal of Neuroscience Research, 2017, 95(9): 1730-1744.

DOI：10.1002/jnr.24002

• neuronal polarity
• axon outgrowth
• mGluR5
• MTEP
• Akt
• NF-kappa B

Metabotropic glutamate receptor 5 (mGluR5) is extensively involved in neural survival, differentiation, dendritic morphology, synaptic plasticity, and neural circuit formation. However, little is known about its role in neuronal polarization and axon outgrowth. In this study, we applied the selective agonist (RS)-2-chloro-5-hydroxyphenylglycine sodium salt and antagonist 3-[(2-methyl-4-thaizolyl)ethynyl] pyridine (MTEP) of mGluR5 to the cultured hippocampal neurons to observe the neuronal polarization and axon outgrowth, and further explored the possible intracellular signal transduction pathway. The results demonstrated that MTEP administration significantly attenuates the proportion of polarized neurons and the length of the axon, indicated by SMI312 (an axon marker) and Tuj-1 (a marker of all the neurites) double-labeling immunofluorescence. Western blot analysis showed that MTEP administration also inhibited the activation of AKT and nuclear translocation of nuclear factor-kappa B (NF-kappa B) p65, and decreased the phosphorylation of p65 as well. Furthermore, Akt inhibitor LY294002 treatment resulted in neuronal polarization delay and axon outgrowth retardation, while suppressing the phosphorylation and nuclear translocation of p65. We concluded that mGluR5 could regulate neuronal polarity and axon outgrowth during the morphological differentiation of rat developing neurons, and the intracellular signaling pathway of Akt-NF-kappa B might be involved in the action of mGluR5.

• 出版日期2017-9
• 单位西安交通大学