Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Institute of Neuroscience, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Brain Behav. 2021 Jan;11(1):e01949. doi: 10.1002/brb3.1949. Epub 2020 Nov 17.
Recent animal studies showed that isoflurane exposure may lead to the disturbance of hippocampal neurogenesis and later cognitive impairment. However, much less is known about the effect of isoflurane exposure on the neurons generated form tertiary dentate matrix, even though a great increase of granule cell population during the infantile period is principally derived from this area.
To label the new cells originated from the tertiary dentate matrix, the mice were injected with BrdU on postnatal day 6 (P6). Then, the mice were exposed to isoflurane for 4 hr at 1, 8, 21, and 42 days after BrdU injection, and the brains were collected 24 hr later. The loss of newly generated cells/neurons with different developmental stage was assessed by BrdU, BrdU + DCX, BrdU + NeuN, or BrdU + Prox-1 staining, respectively.
We found that the isoflurane exposure significantly decreased the numbers of nascent cells (1 day old) and mature neurons (42 days old), but had no effect on the immature (8 days old) and early mature neurons (8 and 21 days old, respectively).
The results suggested isoflurane exposure exerts the neurotoxic effects on the tertiary dentate matrix-originated cells with an age-defined pattern in mice, which partly explain the cognitive impairment resulting from isoflurane exposure to the young brain.
最近的动物研究表明，异氟醚暴露可能导致海马神经发生紊乱和随后的认知障碍。然而，对于异氟醚暴露对来自三级齿状回基质的神经元的影响知之甚少，尽管婴儿期颗粒细胞群体的大量增加主要来自该区域。
为了标记来自三级齿状回基质的新细胞，在出生后第 6 天（P6）给小鼠注射 BrdU。然后，在 BrdU 注射后 1、8、21 和 42 天，将小鼠暴露于异氟醚中 4 小时，24 小时后收集大脑。通过 BrdU、BrdU+DCX、BrdU+NeuN 或 BrdU+Prox-1 染色分别评估不同发育阶段新生成细胞/神经元的丢失。
我们发现异氟醚暴露显著减少了新生细胞（1 天龄）和成熟神经元（42 天龄）的数量，但对未成熟（8 天龄）和早期成熟神经元（分别为 8 天龄和 21 天龄）没有影响。
结果表明，异氟醚暴露对小鼠三级齿状回基质来源的细胞具有年龄定义的神经毒性作用，这部分解释了异氟醚暴露对年轻大脑导致的认知障碍。
