HDAC Inhibitors Induce BDNF Expression and Promote Neurite Outgrowth in Human Neural Progenitor Cells-Derived Neurons

Amir Bagheri, Parham Habibzadeh, Seyedeh Fatemeh Razavipour, Claude Henry Volmar, Nancy T. Chee, Shaun P Brothers, Claes R Wahlestedt, Seyed Javad Mowla, Mohammad A Faghihi

Research output: Contribution to journalArticle

Abstract

Besides its key role in neural development, brain-derived neurotrophic factor (BDNF) is important for long-term potentiation and neurogenesis, which makes it a critical factor in learning and memory. Due to the important role of BDNF in synaptic function and plasticity, an in-house epigenetic library was screened against human neural progenitor cells (HNPCs) and WS1 human skin fibroblast cells using Cell-to-Ct assay kit to identify the small compounds capable of modulating the BDNF expression. In addition to two well-known hydroxamic acid-based histone deacetylase inhibitors (hb-HDACis), SAHA and TSA, several structurally similar HDAC inhibitors including SB-939, PCI-24781 and JNJ-26481585 with even higher impact on BDNF expression, were discovered in this study. Furthermore, by using well-developed immunohistochemistry assays, the selected compounds were also proved to have neurogenic potential improving the neurite outgrowth in HNPCs-derived neurons. In conclusion, we proved the neurogenic potential of several hb-HDACis, alongside their ability to enhance BDNF expression, which by modulating the neurogenesis and/or compensating for neuronal loss, could be propitious for treatment of neurological disorders.

Original languageEnglish (US)
JournalInternational journal of molecular sciences
Volume20
Issue number5
DOIs
StatePublished - Mar 5 2019

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Histone Deacetylase Inhibitors
Brain-Derived Neurotrophic Factor
neurons
inhibitors
Neurons
brain
Brain
Stem Cells
Hydroxamic Acids
cells
Neurogenesis
Assays
Neuronal Plasticity
Aptitude
Acids
Long-Term Potentiation
Fibroblasts
acids
Nervous System Diseases
kits

Keywords

  • BDNF
  • epigenetic library
  • HDAC inhibitor
  • human neural progenitor cell
  • neurite outgrowth
  • neurodegenerative disorder
  • screening

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

HDAC Inhibitors Induce BDNF Expression and Promote Neurite Outgrowth in Human Neural Progenitor Cells-Derived Neurons. / Bagheri, Amir; Habibzadeh, Parham; Razavipour, Seyedeh Fatemeh; Volmar, Claude Henry; Chee, Nancy T.; Brothers, Shaun P; Wahlestedt, Claes R; Mowla, Seyed Javad; Faghihi, Mohammad A.

In: International journal of molecular sciences, Vol. 20, No. 5, 05.03.2019.

Research output: Contribution to journalArticle

Bagheri, Amir ; Habibzadeh, Parham ; Razavipour, Seyedeh Fatemeh ; Volmar, Claude Henry ; Chee, Nancy T. ; Brothers, Shaun P ; Wahlestedt, Claes R ; Mowla, Seyed Javad ; Faghihi, Mohammad A. / HDAC Inhibitors Induce BDNF Expression and Promote Neurite Outgrowth in Human Neural Progenitor Cells-Derived Neurons. In: International journal of molecular sciences. 2019 ; Vol. 20, No. 5.
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