Propofol Administration During Early Postnatal Life Suppresses Hippocampal Neurogenesis
Propofol Administration During Early Postnatal Life Suppresses Hippocampal Neurogenesis
复制标题
产后早期使用异丙酚会抑制海马神经发生。
DOI：
10.1007/s12035-014-9052-7
复制
发表时间：
2016-03-01
影响因子：
5.1
通讯作者：
Fan, Xiaotang
中科院分区：
文献类型：
--
作者：
Huang, Jing;Jing, Sheng;Fan, Xiaotang
丙泊酚是目前应用最广泛的静脉麻醉药之一，已被表明会导致成人认知功能障碍。在此，我们研究了出生后早期接触丙泊酚对海马神经发生的影响。在出生后第7天（P7）或P7 - P9给小鼠施用丙泊酚（30或60 mg/kg）；在P8或P17评估齿状回（DG）的细胞增殖和神经发生。结果显示，在P7接触60 mg/kg丙泊酚会降低海马细胞增殖，这通过P8时BrdU和Sox2免疫染色表明，但30 mg/kg剂量时无此现象。蛋白质印迹显示丙泊酚处理在P8降低了海马中Akt或细胞外信号相关激酶（ERK）1/2的磷酸化。P7至P9的丙泊酚处理减少了P17时DG中新生神经元的数量，同时伴有颗粒神经元成熟延迟以及树突棘密度降低，尤其是蘑菇状成熟棘。此外，体外研究结果表明丙泊酚以剂量依赖的方式抑制C17.2神经干细胞系的细胞增殖和细胞有丝分裂，并激活其凋亡。这些发现表明丙泊酚会损害未成熟小鼠大脑中的细胞增殖并抑制神经发生，因此可能与丙泊酚麻醉诱导的认知功能障碍有关。
Propofol is currently one of the most widely used intravenous anesthetics and has been indicated to induce cognitive dysfunction in adults. Here, we investigated the effects of propofol exposure during early postnatal life on hippocampal neurogenesis. Propofol (30 or 60 mg/kg) was administered to mice on either postnatal day (P) 7 or P7-P9; cell proliferation and neurogenesis in the dentate gyrus (DG) were evaluated on P8 or P17. It showed that exposure to propofol on P7 decreased hippocampal cell proliferation as indicated by BrdU and Sox2 immunostaining at P8 in propofol treatment at the dosage of 60 mg/kg but not at the dosage of 30 mg/kg. Western blots revealed propofol treatment decreased Akt or extracellular signal-related kinase (ERK) 1/2 phosphorylation in the hippocampus at P8. Propofol treatment on P7 to P9 reduced the numbers of newly formed neurons in the DG at P17, which was accompanied by delay of granule neuron maturation and decreased the density of dendritic spines, particularly the mushroom-shaped mature spines. Furthermore, the in vitro findings indicated propofol suppressed cell proliferation and cell mitosis and activated apoptosis of C17.2 neural stem cell line in a dose-dependent manner. These findings suggest that propofol impairs cell proliferation and inhibits neurogenesis in the immature mouse brain and thus is possibly involved in the cognitive dysfunction induced by propofol anesthesia.