Department of Neurology, The Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, 214000, Jiangsu, China.
Department of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Rd, Gusu District, Suzhou, 215004, Jiangsu, China.
Cell Mol Neurobiol. 2018 Aug;38(6):1305-1313. doi: 10.1007/s10571-018-0599-0. Epub 2018 Jun 27.
Minocycline, an anti-infective agent of a tetracycline derivative, is reported to improve behavioral functional recovery after cerebral ischemia via enhancing the levels of brain-derived neurotrophic factor (BDNF). However, the precise mechanisms that minocycline targets to enhance the expression of BDNF are not fully defined. In the present study, we observed the neuroprotective effect and its potential mechanisms of minocycline using oxygen-glucose deprivation/reoxygenation (OGD/R)-treated N2a cells. We found that 50 µM minocycline protected against neuronal apoptosis induced by OGD/R injury, with increased expression ratio of Bcl-2/Bax and reduced expression of caspase-3. Interestingly, minocycline resulted in the up-regulation of only BDNF protein, not BDNF mRNA in N2a cells treated with OGD/R. Furthermore, we found that minocycline inhibited OGD/R-induced up-regulation of miR-155 targeted BDNF transcripts. Moreover, miR-155 mimic could partially abolish the neuroprotective effects of minocycline via inhibiting the levels of BDNF protein. These findings suggest that minocycline is neuroprotective against ischemic brain injury through their modulation of miR-155-mediated BDNF repression.
米诺环素是一种四环抗生素衍生物的抗感染药物，据报道，它通过增加脑源性神经营养因子（BDNF）的水平来改善脑缺血后的行为功能恢复。然而，米诺环素靶向增强 BDNF 表达的确切机制尚未完全确定。在本研究中，我们使用氧葡萄糖剥夺/复氧（OGD/R）处理的 N2a 细胞观察了米诺环素的神经保护作用及其潜在机制。我们发现，50µM 米诺环素可预防 OGD/R 损伤诱导的神经元凋亡，Bcl-2/Bax 的表达比值增加，caspase-3 的表达减少。有趣的是，米诺环素仅导致 OGD/R 处理的 N2a 细胞中 BDNF 蛋白而非 BDNF mRNA 的上调。此外，我们发现米诺环素抑制了 OGD/R 诱导的靶向 BDNF 转录物的 miR-155 的上调。此外，miR-155 模拟物可通过抑制 BDNF 蛋白水平部分消除米诺环素的神经保护作用。这些发现表明，米诺环素通过调节 miR-155 介导的 BDNF 抑制对缺血性脑损伤具有神经保护作用。
