Connexin43, but not connexin30, contributes to adult neurogenesis in the dentate gyrus

Brain Res Bull. 2018 Jan;136:91-100. doi: 10.1016/j.brainresbull.2017.07.001. Epub 2017 Jul 6.

Abstract

The subgranular zone of the dentate gyrus represents a niche in which radial glia (RG)-like cells generate new neurons throughout postnatal life in the mammalian brain. Previous data showed that RG-like cells are coupled through gap junction channels, primarily formed by connexin43 (Cx43) and Cx30, and that the expression of these proteins is required for adult neurogenesis in the hippocampus. However, their individual function and underlying mechanisms remain unclear. Here we demonstrate that Cx43, but not Cx30, is crucial for adult neurogenesis. To assess whether Cx43-dependent intercellular coupling between RG-like cells or rather channel-independent interactions of the protein regulate neurogenesis, mice bearing a Cx43 point mutation (Cx43G138R) in RG-like cells and protoplasmic astrocytes cells were employed, which was expected to cause channel closure without affecting the trafficking of the protein to the membrane. We confirmed the disruption of coupling between RG-like cells and astrocytes in the hippocampus of Cx43G138R mice. Proliferative activity and neurogenesis in the DG were significantly decreased in the mutant mouse line, indicating that functional Cx43 channels are essential for proper adult neurogenesis. The fate of proliferating cells in the DG was not affected by Cx43 mutation as revealed by 5-bromo-2-deoxyuridine (BrdU) incorporation assays. Together, these findings suggest that adult neurogenesis in the hippocampus does not require Cx30 but channel-dependent functions of Cx43.

Keywords: Astrocyte; Cx43; Gap junction; Hippocampus; RG-like cells; Subgranular zone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology
  • Adult Stem Cells / metabolism*
  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism
  • Cell Proliferation / physiology
  • Connexin 30 / genetics
  • Connexin 30 / metabolism*
  • Connexin 43 / genetics
  • Connexin 43 / metabolism*
  • Dentate Gyrus / cytology
  • Dentate Gyrus / metabolism*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neurogenesis / physiology*
  • Point Mutation

Substances

  • Connexin 30
  • Connexin 43
  • GJA1 protein, mouse
  • Gjb6 protein, mouse
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins