Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Molecular Brain Science, Division of Developmental Neuroscience, Department of Child Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University, and University of Fukui (UGSCD), Osaka University, Suita, Osaka, Japan.
J Neurochem. 2021 Nov;159(4):778-788. doi: 10.1111/jnc.15505. Epub 2021 Sep 17.
Corticosteroids are stress-related hormones that maintain homeostasis. The most effective corticosteroids are corticosterone (CORT) in rodents and cortisol in primates. 11β-Hydroxysteroid dehydrogenase type 1 (11β-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.
皮质甾类是维持体内平衡的应激相关激素。最有效的皮质甾类是啮齿动物中的皮质酮（CORT）和灵长类动物中的皮质醇。11β-羟甾类脱氢酶 1 型（11β-HSD1；EC 1.1.1.146），由 Hsd11b1 编码，是 CORT/皮质醇局部浓度的关键调节因子。在成年小鼠的初级体感皮层第 5 层中已经显示出 Hsd11b1 的表达。然而，其在整个新皮层中的定位，特别是在发育过程中的定位，尚未得到充分解决。在这里，我们建立了 Hsd11b1 在发育中的小鼠新皮层中的强大和动态表达谱。发现 Hsd11b1 主要存在于锥体神经元中。通过逆行追踪，我们观察到一些 Hsd11b1 阳性细胞是投射神经元，表明至少有一些是兴奋性的。在出生后第 0 天（P0），Hsd11b1 在体感皮层的深层表达。然后，从 P3 到 P8，表达区域广泛扩展；在第 4 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）。从 P14 开始，阳性区域逐渐变窄，最终在 P26 及以后仅限于体感皮层的第 5 层。此外，我们给哺乳期母鼠注射 CORT 以增加其幼崽的系统 CORT 水平。在这里，我们观察到这些幼崽的新皮层中 Hsd11b1 阳性细胞数量减少。我们的观察表明，发育中的新皮层中 Hsd11b1 的表达受到系统 CORT 水平的影响。母亲的压力可能会影响其孩子的新皮层发育。
