Transient expansion of the expression region of Hsd11b1, encoding 11β-hydroxysteroid dehydrogenase type 1, in the developing mouse neocortex
Transient expansion of the expression region of Hsd11b1, encoding 11β-hydroxysteroid dehydrogenase type 1, in the developing mouse neocortex
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DOI：
10.1111/jnc.15505
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发表时间：
2021-09-17
影响因子：
4.7
通讯作者：
Sato, Makoto
中科院分区：
文献类型：
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作者：
Doi, Miyuki;Oka, Yuichiro;Sato, Makoto
皮质类固醇是与压力相关的激素，维持体内平衡。最有效的皮质类固醇是啮齿类动物的皮质酮（CORT）和灵长类动物的皮质醇。由Hsd 11b 1编码的11 β-羟基类固醇脱氢酶1型（11 β-HSD 1; EC 1.1.1.146）是CORT/皮质醇局部浓度的关键调节剂。在成年小鼠的初级躯体感觉皮层的第5层中hsd 11b 1的表达已经被证明。然而，它在整个新皮层中的定位，特别是在发育过程中，尚未得到充分解决。在这里，我们建立了强大的和动态的Hsd 11b 1在发育中的小鼠新皮层的表达谱。Hsd 11b 1主要分布于锥体神经元。通过逆行追踪，我们观察到一些Hsd 11b 1阳性细胞是投射神经元，表明至少有一些是兴奋性的。出生后0天（P0），Hsd 11b 1在躯体感觉皮层深层表达。然后，从P3到P8，表达区域广泛扩展，在第4层和第5层观察到，跨越整个新皮层，包括初级运动皮层（M1）和初级视觉皮层（V1）。阳性区域从P14开始逐渐变窄，并最终在P26及以后局限于躯体感觉皮层的第5层。此外，我们管理的CORT哺乳母鼠，以增加其幼崽的全身CORT水平。在这里，我们观察到这些幼崽的新皮层中Hsd 11b 1阳性细胞的数量减少。我们的观察表明，Hsd 11b 1在发育中的新皮层的表达受到全身CORT水平的影响。母亲的压力可能会影响孩子的大脑皮层发育。
Corticosteroids are stress-related hormones that maintain homeostasis. The most effective corticosteroids are corticosterone (CORT) in rodents and cortisol in primates. 11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1; EC 1.1.1.146), encoded by Hsd11b1, is a key regulator of the local concentration of CORT/cortisol. Hsd11b1 expression in layer 5 of the primary somatosensory cortex has been shown in adult mice. However, its localization in the entire neocortex, especially during development, has not been fully addressed. Here, we established robust and dynamic expression profiles of Hsd11b1 in the developing mouse neocortex. Hsd11b1 was found mostly in pyramidal neurons. By retrograde tracing, we observed that some Hsd11b1-positive cells were projection neurons, indicating that at least some were excitatory. At postnatal day 0 (P0), Hsd11b1 was expressed in the deep layer of the somatosensory cortex. Then, from P3 to P8, the expression area expanded broadly; it was observed in layers 4 and 5, spanning the whole neocortex, including the primary motor cortex (M1) and the primary visual cortex (V1). The positive region gradually narrowed from P14 onwards and was ultimately limited to layer 5 of the somatosensory cortex at P26 and later. Furthermore, we administered CORT to nursing dams to increase the systemic CORT level of their pups. Here, we observed a reduced number of Hsd11b1-positive cells in the neocortex of these pups. Our observation suggests that Hsd11b1 expression in the developing neocortex is affected by systemic CORT levels. It is possible that stress on mothers influences the neocortical development of their children.