PUBLICATION

Histone deacetylase inhibition promotes regenerative neurogenesis after stab wound injury in the adult zebrafish optic tectum

Authors
Kiyooka, M., Shimizu, Y., Ohshima, T.
ID
ZDB-PUB-200728-2
Date
2020
Source
Biochemical and Biophysical Research Communications   529: 366-371 (Journal)
Registered Authors
Ohshima, Toshio, Shimizu, Yuki
Keywords
Brain regeneration, Histone deacetylase, Optic tectum, Radial glial cell, Stab wound injury, Zebrafish
MeSH Terms
  • Animals
  • Cell Proliferation/drug effects
  • Female
  • Histone Deacetylase Inhibitors/pharmacology*
  • Histone Deacetylase Inhibitors/therapeutic use
  • Hydroxamic Acids/pharmacology*
  • Hydroxamic Acids/therapeutic use
  • Male
  • Nerve Regeneration/drug effects*
  • Neurogenesis/drug effects
  • Superior Colliculi/drug effects
  • Superior Colliculi/injuries*
  • Superior Colliculi/physiology
  • Superior Colliculi/physiopathology
  • Wounds, Stab/drug therapy*
  • Wounds, Stab/physiopathology
  • Zebrafish/physiology*
PubMed
32703437 Full text @ Biochem. Biophys. Res. Commun.
Abstract
The central nervous system (CNS) of adult zebrafish is capable of recovering from injury, unlike the CNS of mammals such as humans or rodents. Previously, we established a stab wound injury model of the optic tectum (OT) in the adult zebrafish and showed that the radial glial cells (RG) proliferation and neuronal differentiation contributes to OT regeneration. In the present study, we analyzed the function of histone deacetylases (HDACs) as potential regulators of OT regeneration. The expression of both hdac1 and hdac3 was found to be significantly decreased in the injured OT. In order to analyze the roles of HDACs in RG proliferation and differentiation after injury, we performed pharmacological experiments using the HDAC inhibitor trichostatin A. We found that HDAC inhibition after stab wound injury suppressed RG proliferation but promoted neuronal differentiation. Moreover, HDAC inhibition suppressed the injury-induced decline in expression of Notch signaling target genes, her4.1 and her6 after OT injury. These results suggest that HDACs regulate regenerative neurogenesis through changes in Notch target gene expression by histone deacetylation. HDACs and histone acetylation are promising molecular targets for neuronal regeneration and further studies about the molecular mechanisms behind the regulation of regeneration by histone acetylation are necessary.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping