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

Mariko Kiyooka, Yuki Shimizu, Toshio Ohshima

Biochemical and biophysical research communications 2020 Aug 20

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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. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Mariko Kiyooka, Yuki Shimizu, Toshio Ohshima. Histone deacetylase inhibition promotes regenerative neurogenesis after stab wound injury in the adult zebrafish optic tectum. Biochemical and biophysical research communications. 2020 Aug 20;529(2):366-371