Hippocampal Neurogenesis Requires Cell-Autonomous Thyroid Hormone Signaling

Stem Cell Reports. 2020 May 12;14(5):845-860. doi: 10.1016/j.stemcr.2020.03.014. Epub 2020 Apr 16.

Abstract

Adult hippocampal neurogenesis is strongly dependent on thyroid hormone (TH). Whether TH signaling regulates this process in a cell-autonomous or non-autonomous manner remains unknown. To answer this question, we used global and conditional knockouts of the TH transporter monocarboxylate transporter 8 (MCT8), having first used FACS and immunohistochemistry to demonstrate that MCT8 is the only TH transporter expressed on neuroblasts and adult slice cultures to confirm a necessary role for MCT8 in neurogenesis. Both mice with a global deletion or an adult neural stem cell-specific deletion of MCT8 showed decreased expression of the cell-cycle inhibitor P27KIP1, reduced differentiation of neuroblasts, and impaired generation of new granule cell neurons, with global knockout mice also showing enhanced neuroblast proliferation. Together, our results reveal a cell-autonomous role for TH signaling in adult hippocampal neurogenesis alongside non-cell-autonomous effects on cell proliferation earlier in the lineage.

Keywords: MCT8; P27KIP1; Slc16a2; T3; T4; adult hippocampal neurogenesis; neuroblasts; thyroid hormone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Hippocampus / cytology
  • Hippocampus / growth & development*
  • Hippocampus / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Monocarboxylic Acid Transporters / genetics
  • Monocarboxylic Acid Transporters / metabolism*
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neurogenesis*
  • Signal Transduction
  • Symporters / genetics
  • Symporters / metabolism*
  • Thyroid Hormones / metabolism*

Substances

  • Cdkn1b protein, mouse
  • Monocarboxylic Acid Transporters
  • Slc16a2 protein, mouse
  • Symporters
  • Thyroid Hormones
  • Cyclin-Dependent Kinase Inhibitor p27