Transient expansion of the expression region of Hsd11b1, encoding 11β-hydroxysteroid dehydrogenase type 1, in the developing mouse neocortex

J Neurochem. 2021 Nov;159(4):778-788. doi: 10.1111/jnc.15505. Epub 2021 Sep 17.

Abstract

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.

Keywords: cortex; corticosterone; cortisol; development; mother-child relationship; stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / biosynthesis*
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / genetics*
  • Animals
  • Corticosterone / pharmacology
  • Denervation
  • Female
  • Gene Expression
  • Mice
  • Mice, Inbred ICR
  • Motor Cortex / growth & development
  • Motor Cortex / metabolism
  • Neocortex / growth & development
  • Neocortex / metabolism*
  • Neurons / metabolism
  • Pregnancy
  • Pyramidal Cells / metabolism
  • Somatosensory Cortex / metabolism
  • Vibrissae / innervation
  • Visual Cortex / growth & development
  • Visual Cortex / metabolism

Substances

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • Corticosterone