Neuroprotective role of minocycline in co-cultures of human fetal neurons and microglia
Neuroprotective role of minocycline in co-cultures of human fetal neurons and microglia
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DOI：
10.1016/j.expneurol.2007.12.024
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发表时间：
2008-05-01
影响因子：
5.3
通讯作者：
Zecevic, Nada
中科院分区：
文献类型：
--
作者：
Fillpovic, Radmila;Zecevic, Nada
妊娠期细菌感染常导致早产和新生儿白质损伤。在这些感染中，中枢神经系统的常驻免疫细胞小胶质细胞被激活，并导致中枢神经系统的进一步神经元损伤。二甲胺四环素是一种第二代四环素抗生素，可以抑制啮齿动物的小胶质细胞激活并保护神经元，但有关其对人类细胞影响的数据有限。我们研究了米诺环素在脂多糖（LPS）诱导的炎症过程中对人胎儿脑小胶质细胞和神经元的纯化细胞培养或共培养中的神经保护作用机制。在神经元/小胶质共培养中，二甲胺四环素治疗可以阻止小胶质细胞的活化和增殖，并保护神经元，这可以通过减少神经元细胞死亡和Bcl-2家族蛋白向抗凋亡比例的转变来证明。值得注意的是，在纯化的神经元培养物中，米诺环素和LPS对神经元都没有影响。二甲胺四环素调节人胎儿小胶质细胞激活的能力可能与用于治疗新生儿中枢神经系统感染的疗法有关。(C) 2008爱思唯尔公司版权所有。
Bacterial infections during pregnancy often result in premature birth and neonatal white matter damage. During these infections, microglia, the resident immune cells of the CNS, undergo activation and contribute to further neuronal damage of the CNS. Minocycline, a second-generation tetracycline antibiotic, inhibits microglial activation and protects neurons in rodents but data about its effects on human cells are limited. We studied the mechanism of the neuroprotective effect of minocycline in either purified cell cultures or co-cultures of microglia and neurons from human fetal brain during inflammation induced by lipopolysaccharide (LPS). In neuron/microglial co-cultures, minocycline treatment prevented activation and proliferation of microglia and protected neurons as demonstrated by decreased neuronal cell death and a shift of Bcl-2 family proteins toward anti-apoptotic ratio. Notably, neither minocycline nor LPS had an effect on neurons in purified neuronal cultures. The ability of minocycline to regulate activation of human fetal microglia might be relevant in therapies used towards treating neonatal CNS infections. (C) 2008 Elsevier Inc. All rights reserved.