Minocycline attenuates the development of diabetic neuropathy by inhibiting spinal cord Notch signaling in rat
| Autor: | Jie Gao, Yonghao Yu, Cheng Yang, Nuo Yan, Jiamin Liang, Yufei Kan, Yiqing Ren, Yang Jiao, Hui Li, Banglin Wu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Diabetic neuropathy Neural Conduction Minocycline Pharmacology Nerve conduction velocity Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Diabetic Neuropathies Sural Nerve medicine Animals Receptors Notch Microglia business.industry Body Weight Dipeptides General Medicine medicine.disease Spinal cord Streptozotocin Glucose 030104 developmental biology medicine.anatomical_structure Spinal Cord Anesthesia Neuropathic pain Sciatic nerve business 030217 neurology & neurosurgery Signal Transduction medicine.drug |
| Zdroj: | Biomedicine & Pharmacotherapy. 94:380-385 |
| ISSN: | 0753-3322 |
| DOI: | 10.1016/j.biopha.2017.07.078 |
| Popis: | We studied the effects of minocycline (an inhibitor of microglial activation) on the expression and activity of Notch-1 receptor, and explored the therapeutic efficacy of minocycline combined with Notch inhibitor DAPT in the treatment of diabetic neuropathic pain (DNP). Diabetic rat model was established by intraperitoneal injection (ip) of Streptozotocin (STZ). Expression and activity of Notch-1 and expression of macrophage/microglia marker Iba-1 were detected by WB. Diabetes induction significantly attenuated sciatic nerve conduction velocity, and dramatically augmented the expression and the activity of Notch-1 in the lumbar enlargement of the spinal cord. Minocycline treatment, however, accelerated the decreased conduction velocity of sciatic nerve and suppressed Notch-1expression and activity in diabetic rats. Similar to DAPT treatment, minocycline administration also prolonged thermal withdrawal latency (TWL) and increase mechanical withdrawal threshold (MWT) in diabetic rats in response to heat or mechanical stimulation via inhibition the expression and the activity of Notch-1 in spinal cord. Combination of DAPT and minocycline further inhibited Notch-1 receptor signaling and reduce neuropathic pain exhibited as improved TWL and MWT. Our study revealed a novel mechanism of Notch-1 receptor inhibition in spinal cord induced by minocycline administration, and suggested that the combination of minocycline and DAPT has the potential to treat DNP. |
| Databáze: | OpenAIRE |
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