Prenatal exposure to suberoylanilide hydroxamic acid perturbs corticogenesis

Nunung Yuniarti, Berry Juliandi, Chai MuhChyi, Hirofumi Noguchi, Tsukasa Sanosaka, Kinichi Nakashima

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Suberoylanilide hydroxamic acid (SAHA) is one of the epidrugs developed for cancer treatment that works epigenetically by inhibiting histone deacetylases (HDACs). SAHA has been reported to diffuse across the placenta and found in fetal plasma in preclinical study, implying that it can influence fetus if taken by pregnant cancer patients. However, report regarding this aspect and the study of in utero HDAC inhibition by SAHA especially on fate specification of neural stem/progenitor cells within the developing mammalian cortex, is yet unavailable. Here we show that transient exposure of SAHA to mouse embryos during prominent neurogenic period resulted in an enhancement of cortical neurogenesis, which is accompanied by an increased expression of proneuronal transcription factor Neurog1. Neurogenesis was enhanced due to the increase number of proliferating Tbr2+ intermediate progenitor cells following SAHA exposure. In this relation, we observed that SAHA perturbed neonatal cortical lamination because of the increased production of Cux1+ and Satb2+ upper-layer neurons, and decreased that of Ctip2+ deep-layer neurons. Furthermore, an upper-layer neuronal lineage determinant Satb2 was also up-regulated, whereas those of deep-layer ones Fezf2 and Ctip2 were down-regulated by SAHA treatment. Taken together, our study suggests that proper regulation of HDACs is important for precise embryonic corticogenesis.

Original languageEnglish
Pages (from-to)42-49
Number of pages8
JournalNeuroscience Research
Volume77
Issue number1-2
DOIs
Publication statusPublished - 2013 Sep
Externally publishedYes

Fingerprint

Histone Deacetylases
Neurogenesis
Stem Cells
Neurons
Neural Stem Cells
vorinostat
Placenta
Neoplasms
Fetus
Transcription Factors
Embryonic Structures
Therapeutics

Keywords

  • Corticogenesis
  • HDAC inhibitor
  • Histone acetylation
  • Neural stem cells
  • Neurogenesis
  • SAHA

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Prenatal exposure to suberoylanilide hydroxamic acid perturbs corticogenesis. / Yuniarti, Nunung; Juliandi, Berry; MuhChyi, Chai; Noguchi, Hirofumi; Sanosaka, Tsukasa; Nakashima, Kinichi.

In: Neuroscience Research, Vol. 77, No. 1-2, 09.2013, p. 42-49.

Research output: Contribution to journalArticle

Yuniarti, N, Juliandi, B, MuhChyi, C, Noguchi, H, Sanosaka, T & Nakashima, K 2013, 'Prenatal exposure to suberoylanilide hydroxamic acid perturbs corticogenesis', Neuroscience Research, vol. 77, no. 1-2, pp. 42-49. https://doi.org/10.1016/j.neures.2013.06.004
Yuniarti, Nunung ; Juliandi, Berry ; MuhChyi, Chai ; Noguchi, Hirofumi ; Sanosaka, Tsukasa ; Nakashima, Kinichi. / Prenatal exposure to suberoylanilide hydroxamic acid perturbs corticogenesis. In: Neuroscience Research. 2013 ; Vol. 77, No. 1-2. pp. 42-49.
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