| Autor: |
Jia-Hui, Lu, Mao-Biao, Zhang, Jun-Wu, Wang, Xiu-Ying, Ye, Jia-Li, Chen, Gai-Li, Jia, Ci-Shan, Xie, Yu-Jing, Shen, Yuan-Xiang, Tao, Jun, Li, Hong, Cao |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Am J Transl Res |
| ISSN: |
1943-8141 |
| Popis: |
Objective: Diabetic neuropathic pain (DNP) is one of the common complications in type 2 Diabetes Mellitus (DM) patients. However, molecular mechanisms in underlying diabetic neuropathic pain are still poorly understood. Kalirin-7, a multifunctional Rho GDP/GTP exchange factor, located at the excitatory synapses, was reported to modulate the neuronal cytoskeleton. Therefore, in this study, we explored the effects of Kalirin-7 on type 2 diabetic neuropathic pain and the mechanisms in spinal cord in rats. Methods: The type 2 diabetic neuropathic pain model was established in rats by feeding them with a high-sugar and high-fat diet for 8 weeks, and then fasting them for 12 hours, followed by a single intraperitoneal injection of STZ. Kalirin-7 was knocked down in the spinal cord by an intrathecal administration of Kalirin-7 siRNA. Results: The levels of Kalirin-7, p-NR2B and PSD-95 as well as the PSD-95-NR2B coupling were significantly increased in the spinal cord of type 2 DM rats. The knockdown of Kalirin-7 expression in the spinal cord by the intrathecal administration of Kalirin-7 siRNA not only reduced the levels of p-NR2B and the PSD-95-NR2B coupling in the spinal cord, but also relieved mechanical allodynia and thermal hyperalgesia in type 2 DM rats. Conclusions: Our findings suggest that spinally expressed Kalirin-7 likely contributes to type 2 diabetic neuropathic pain through regulating the PSD-95/NR2B interaction-dependent NR2B phosphorylation in the spinal cord. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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