Immature murine hippocampal neurones do not develop long-term structural changes after a single isoflurane exposure
Immature murine hippocampal neurones do not develop long-term structural changes after a single isoflurane exposure
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DOI：
10.1016/j.bja.2019.08.019
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发表时间：
2019-12-01
影响因子：
9.8
通讯作者：
Danzer, Steve C.
中科院分区：
文献类型：
--
作者：
Tong, Dongyi;Godale, Christin M.;Danzer, Steve C.
背景：在发育中的动物中的研究表明，临床相关的麻醉暴露会增加神经元死亡并改变大脑结构。在海马齿状回，麻醉剂异氟醚诱导21天龄小鼠约10%的2周龄海马区颗粒细胞选择性凋亡。在这项工作中，我们质疑在暴露中存活的90%的颗粒细胞是否可能受到损伤并异常整合到大脑中。方法：采用转基因小鼠模型命运图方法，研究异氟烷暴露对颗粒细胞结构的长期影响，以识别和标记未成熟的颗粒细胞。雄性和雌性小鼠在命运映射颗粒细胞2周龄时暴露于异氟醚6h。结果：异氟醚处理不影响齿状回的大体结构，颗粒细胞出现在正确的亚区。单独的异氟醚暴露的颗粒细胞结构正常，在棘突密度、棘突类型、树突长度或突触前轴突终末结构方面没有变化(P>；0.05)。雌性小鼠的颗粒细胞轴突终末比雄性大13%；然而，无论治疗方法如何，这种差异都是明显的(均值差=0.955；95%可信区间0.371.5；P=0.010)。结论：单一的、长期的异氟醚暴露不会损害这一年龄特定的颗粒细胞队列的整合，无论动物的性别。尽管如此，尽管2周大的细胞没有受到影响，但结果不应该推断到其他年龄组，因为其他年龄组可能会有不同的反应。
Background: Studies in developing animals show that a clinically relevant anaesthesia exposure increases neuronal death and alters brain structure. In the hippocampal dentate gyrus, the anaesthetic isoflurane induces selective apoptosis among roughly 10% of 2-week-old hippocampal granule cells in 21-day-old mice. In this work, we queried whether the 90% of granule cells surviving the exposure might be 'injured' and integrate abnormally into the brain.Methods: The long-term impact of isoflurane exposure on granule cell structure was studied using a transgenic mouse model fate-mapping approach to identify and label immature granule cells. Male and female mice were exposed to isoflurane for 6 h when the fate-mapped granule cells were 2 weeks old. The morphology of the fate-mapped granule cells was quantified 2 months later.Results: The gross structure of the dentate gyrus was not affected by isoflurane treatment, with granule cells present in the correct subregions. Individual isoflurane-exposed granule cells were structurally normal, exhibiting no changes in spine density, spine type, dendrite length, or presynaptic axon terminal structure (P>0.05). Granule cell axon terminals were 13% larger in female mice relative to males; however, this difference was evident regardless of treatment (difference of means=0.955; 95% confidence interval, 0.37-1.5; P=0.010).Conclusions: A single, prolonged isoflurane exposure did not impair integration of this age-specific cohort of granule cells, regardless of the animal's sex. Nonetheless, although 2-week-old cells were not affected, the results should not be extrapolated to other age cohorts, which may respond differently.