RRC ID 65574
Author Dozawa M, Kono H, Sato Y, Ito Y, Tanaka H, Ohshima T.
Title Valproic acid, a histone deacetylase inhibitor, regulates cell proliferation in the adult zebrafish optic tectum.
Journal Dev Dyn
Abstract BACKGROUND:Valproic acid (VPA) has been used to treat epilepsy and bipolar disorder. Several reports have demonstrated that VPA functions as a histone deacetylase (HDAC) inhibitor. While VPA is known to cause teratogenic changes in the embryonic zebrafish brain, its effects on neural stem cells (NSCs) in both the embryonic and adult zebrafish are not well understood.
RESULTS:In this study, we observed a proliferative effect of VPA on NSCs in the embryonic hindbrain. In contrast, VPA reduced cell proliferation in the adult zebrafish optic tectum. Treatment with HDAC inhibitors showed a similar inhibitory effect on cell proliferation in the adult zebrafish optic tectum, suggesting that VPA reduces cell proliferation through HDAC inhibition. Cell cycle progression was also suppressed in the optic tectum of the adult zebrafish brain because of HDAC inhibition. Recent studies have demonstrated that HDAC inhibits the Notch signaling pathway; hence, adult zebrafish were treated with a Notch inhibitor. This increased the number of proliferating cells in the adult zebrafish optic tectum with down-regulated expression of her4, a target of Notch signaling.
CONCLUSIONS:These results suggest that VPA inhibits HDAC activity and upregulates Notch signaling to reduce cell proliferation in the optic tectum of adult zebrafish.
Volume 243(11)
Pages 1401-15
Published 2014-11-1
DOI 10.1002/dvdy.24173
PMID 25091230
MeSH Animals Basic Helix-Loop-Helix Transcription Factors / metabolism Blotting, Western Bromodeoxyuridine Cell Cycle / drug effects Cell Cycle / physiology Cell Proliferation / drug effects* Cell Proliferation / physiology DNA Primers / genetics Gene Expression Regulation / drug effects Histone Deacetylase Inhibitors / pharmacology* Immunohistochemistry In Situ Hybridization, Fluorescence In Situ Nick-End Labeling Neural Stem Cells / drug effects* Real-Time Polymerase Chain Reaction Receptors, Notch / metabolism Signal Transduction / drug effects Superior Colliculi / cytology* Superior Colliculi / drug effects Valproic Acid / pharmacology* Zebrafish / metabolism Zebrafish / physiology* Zebrafish Proteins / metabolism
IF 3.275
Zebrafish RIKEN WT