The mechanisms by which exposure of the late-stage progenitor cells to the anesthesia sevoflurane alters their differentiation are not known. We seek to query whether the effects of sevoflurane on late-stage progenitor cells might be regulated by apoptosis and/or autophagy.

To address the short-term impact of sevoflurane exposure on granule cell differentiation, we used 5-bromo-2-deoxyuridine (BrdU) to identify the labeled late-stage progenitor granule cells. Male or female rats were exposed to 3% sevoflurane for 4 h when the labeled granule cells were 2 weeks old. Differentiation of the BrdU-labeled granule cells was quantified 4 and 7 days after exposure by double immunofluorescence. The expression of apoptosis and autophagy in hippocampal dentate gyrus (DG) was determined by western blot and immunofluorescence. Western blot for the expression of NF-κB was used to evaluate the mechanism. Morris water maze (MWM) test was performed to detect cognitive function in the rats on postnatal 28–33 days.

Exposure to sevoflurane decreased the differentiation of the BrdU-labeled late-stage progenitor granule cells, but increased the expression of caspase-3, autophagy, and phosphorylated-P65 in the hippocampus of juvenile rats and resulted in cognitive deficiency. These damaging effects of sevoflurane could be mitigated by inhibitors of autophagy, apoptosis, and NF-κB. The increased apoptosis could be alleviated by pretreatment with the autophagy inhibitor 3-MA, and the increased autophagy and apoptosis could be reduced by pretreatment with NF-κB inhibitor BAY 11-7085.

These findings suggest that a single, prolonged sevoflurane exposure could impair the differentiation of late-stage progenitor granule cells in hippocampal DG and cause cognitive deficits possibly via apoptosis activated by autophagy through NF-κB signaling. Our results do not preclude the possibility that the affected differentiation and functional deficits may be caused by depletion of the progenitors pool.

晚期祖细胞暴露于麻醉七氟醚改变其分化的机制尚不清楚。我们试图询问七氟醚对晚期祖细胞的影响是否可能受到细胞凋亡和/或自噬的调节。

为了解决七氟醚暴露对颗粒细胞分化的短期影响，我们使用 5-bromo-2-deoxyuridine (BrdU) 来识别标记的晚期祖颗粒细胞。当标记的颗粒细胞 2 周大时，雄性或雌性大鼠暴露于 3% 七氟醚 4 小时。在暴露后 4 天和 7 天，通过双重免疫荧光对 BrdU 标记的颗粒细胞的分化进行量化。通过蛋白质印迹和免疫荧光测定海马齿状回（DG）中细胞凋亡和自噬的表达。NF-κB表达的Western印迹用于评估机制。进行莫里斯水迷宫 (MWM) 测试以检测大鼠出生后 28-33 天的认知功能。

暴露于七氟醚降低了BrdU标记的晚期祖颗粒细胞的分化，但增加了幼鼠海马中caspase-3、自噬和磷酸化-P65的表达，并导致认知缺陷。七氟醚的这些破坏作用可以通过自噬、细胞凋亡和 NF-κB 的抑制剂来减轻。用自噬抑制剂 3-MA 预处理可以缓解增加的细胞凋亡，用 NF-κB 抑制剂 BAY 11-7085 预处理可以减少增加的自噬和细胞凋亡。

这些研究结果表明，单一、长时间的七氟醚暴露可能会损害海马 DG 中晚期祖颗粒细胞的分化，并可能通过自噬通过 NF-κB 信号传导激活的细胞凋亡导致认知缺陷。我们的结果并不排除受影响的分化和功能缺陷可能是由祖细胞库的消耗引起的。