Minocycline exacerbates apoptotic neurodegeneration induced by the NMDA receptor antagonist MK-801 in the early postnatal mouse brain
Minocycline exacerbates apoptotic neurodegeneration induced by the NMDA receptor antagonist MK-801 in the early postnatal mouse brain
复制标题
DOI：
10.1007/s00406-015-0649-2
复制
发表时间：
2016-10
影响因子：
4.7
通讯作者：
I. Inta;M. Vogt;Anne S. Vogel;M. Bettendorf;P. Gass;D. Inta
中科院分区：
文献类型：
--
作者：
I. Inta;M. Vogt;Anne S. Vogel;M. Bettendorf;P. Gass;D. Inta
NMDA受体（NMDAR）拮抗剂诱导围产期啮齿动物皮质细胞凋亡和延长的精神分裂症样改变通过抗精神病治疗改善。广谱抗生素米诺环素具有抗精神病和神经保护作用。在这里，我们测试了二甲胺四环素是否也能防止NMDAR拮抗剂MK-801在出生后第7天引发的细胞凋亡。令人惊讶的是，二甲胺四环素诱导广泛的皮质细胞凋亡并加剧mk -801引发的细胞死亡。在一些区域，如耻骨下，米诺环素的促凋亡作用甚至比MK-801更明显。这些数据揭示了米诺环素在抗精神病药物中独特的促细胞凋亡特性，引起了对大脑发育和儿童使用后果的关注。
NMDA receptor (NMDAR) antagonists induce in perinatal rodent cortical apoptosis and protracted schizophrenia-like alterations ameliorated by antipsychotic treatment. The broad-spectrum antibiotic minocycline elicits antipsychotic and neuroprotective effects. Here we tested, if minocycline protects also against apoptosis triggered by the NMDAR antagonist MK-801 at postnatal day 7. Surprisingly, minocycline induced widespread cortical apoptosis and exacerbated MK-801-triggered cell death. In some areas such as the subiculum, the pro-apoptotic effect of minocycline was even more pronounced than that elicited by MK-801. These data reveal among antipsychotics unique pro-apoptotic properties of minocycline, raising concerns regarding consequences for brain development and the use in children.