Valproic acid, a histone deacetylase inhibitor, regulates cell proliferation in the adult zebrafish optic tectum

Miki Dozawa, Hiromitsu Kono, Yuki Sato, Yoko Ito, Hideomi Tanaka, Toshio Ohshima

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)1401-1415
    Number of pages15
    JournalDevelopmental Dynamics
    Volume243
    Issue number11
    DOIs
    Publication statusPublished - 2014 Nov 1

    Fingerprint

    Histone Deacetylase Inhibitors
    Superior Colliculi
    Valproic Acid
    Zebrafish
    Cell Proliferation
    Histone Deacetylases
    Neural Stem Cells
    Rhombencephalon
    Brain
    Bipolar Disorder
    Epilepsy
    Cell Cycle
    Up-Regulation
    Cell Count

    Keywords

    • Adult neurogenesis
    • HDAC
    • Optic tectum
    • VPA
    • Zebrafish

    ASJC Scopus subject areas

    • Developmental Biology

    Cite this

    Valproic acid, a histone deacetylase inhibitor, regulates cell proliferation in the adult zebrafish optic tectum. / Dozawa, Miki; Kono, Hiromitsu; Sato, Yuki; Ito, Yoko; Tanaka, Hideomi; Ohshima, Toshio.

    In: Developmental Dynamics, Vol. 243, No. 11, 01.11.2014, p. 1401-1415.

    Research output: Contribution to journalArticle

    Dozawa, Miki ; Kono, Hiromitsu ; Sato, Yuki ; Ito, Yoko ; Tanaka, Hideomi ; Ohshima, Toshio. / Valproic acid, a histone deacetylase inhibitor, regulates cell proliferation in the adult zebrafish optic tectum. In: Developmental Dynamics. 2014 ; Vol. 243, No. 11. pp. 1401-1415.
    @article{bdeeaf10ceeb4696bfa80fe5901153fe,
    title = "Valproic acid, a histone deacetylase inhibitor, regulates cell proliferation in the adult zebrafish optic tectum",
    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.",
    keywords = "Adult neurogenesis, HDAC, Optic tectum, VPA, Zebrafish",
    author = "Miki Dozawa and Hiromitsu Kono and Yuki Sato and Yoko Ito and Hideomi Tanaka and Toshio Ohshima",
    year = "2014",
    month = "11",
    day = "1",
    doi = "10.1002/dvdy.24173",
    language = "English",
    volume = "243",
    pages = "1401--1415",
    journal = "Developmental Dynamics",
    issn = "1058-8388",
    publisher = "Wiley-Liss Inc.",
    number = "11",

    }

    TY - JOUR

    T1 - Valproic acid, a histone deacetylase inhibitor, regulates cell proliferation in the adult zebrafish optic tectum

    AU - Dozawa, Miki

    AU - Kono, Hiromitsu

    AU - Sato, Yuki

    AU - Ito, Yoko

    AU - Tanaka, Hideomi

    AU - Ohshima, Toshio

    PY - 2014/11/1

    Y1 - 2014/11/1

    N2 - 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.

    AB - 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.

    KW - Adult neurogenesis

    KW - HDAC

    KW - Optic tectum

    KW - VPA

    KW - Zebrafish

    UR - http://www.scopus.com/inward/record.url?scp=84908664568&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84908664568&partnerID=8YFLogxK

    U2 - 10.1002/dvdy.24173

    DO - 10.1002/dvdy.24173

    M3 - Article

    VL - 243

    SP - 1401

    EP - 1415

    JO - Developmental Dynamics

    JF - Developmental Dynamics

    SN - 1058-8388

    IS - 11

    ER -