Metabotropic Glutamate Receptor 5 Regulates Synaptic Plasticity in a Chronic Migraine Rat Model Through the PKC/NR2B Signal [post]

Yingying Niu, Xiaoxu Zeng, Lilin Zhao, Yang Zhou, Guangcheng Qin, Dunke Zhang, Qingqing Fu, Jiying Zhou, Li-Xue Chen
2020 unpublished
Background: The mechanism of chronic migraine(CM) is complex, central sensitization is considered as one of the pathological mechanism. Synaptic plasticity is the basis of the central sensitization. Metabotropic glutamate receptor 5 (mGluR5) plays a vital role in the synaptic plasticity of the central nervous system. However, whether mGluR5 can promote the central sensitization by regulating synaptic plasticity in CM is unknown. Methods: Male Wistar rats were used to establish a CM rat model,
more » ... h a CM rat model, and the expression of mGluR5 mRNA and protein were detected by qRT-PCR and western blotting. The allodynia was assessed by mechanical and thermal thresholds, and central sensitization was assessed by expression of the phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) at Serine 133(pCREB-S133)and c-Fos. The synaptic-associated protein postsynaptic density protein 95 (PSD), synaptophysin (Syp), and synaptophysin-1(Syt-1) and synaptic ultrastructure were detected to explore synaptic plasticity. Results: We found that the expression of mGluR5 was upregulated in CM rats. Downregulated the mGluR5 with MPEP alleviated the allodynia and central sensitization. Moreover, mGluR5 regulated the synaptic plasticity by PKC/NR2B signal. Conclusions: These results indicate that mGluR5 contributed to central sensitization by regulating synaptic plasticity in CM through the PKC/NR2B signal, which suggests that mGluR5 may be a potential therapeutic candidate for CM.
doi:10.21203/rs.3.rs-84035/v1 fatcat:wuyt3aqxebcqphqx4b62capimq