Dibutyl phthalate impairs neural progenitor cell proliferation and hippocampal neurogenesis

Wonjong Lee, Jung Hyun Cho, Yujeong Lee, Seulah Lee, Dae Hyun Kim, Sugyeong Ha, Yoshitaka Kondo, Akihito Ishigami, Hae Young Chung, Jaewon Lee

Research output: Contribution to journalArticle

Abstract

Dibutyl phthalate (DBP) is commonly used plasticizer and a known endocrine disruptor that can cause birth defects and developmental disorders. Although several studies have reported that DBP has neurotoxic effects on neurite outgrowth and on learning and memory, its neurotoxic effects on neural progenitor cells (NPCs) have not been investigated. The present study was undertaken to determine the effects of DBP on NPCs and hippocampal neurogenesis. At high concentration DBP (500 μM) retarded NPC proliferation without affecting cell viability by arresting the cell cycle at G1 but did not cause cell death. DNA damage was observed by examining p53 expression and by γH2AX staining. DBP-treated cells had elevated ROS levels and exhibited mitochondrial dysfunction, which can cause DNA damage. Adult hippocampal neurogenesis was investigated using BrdU immunohistochemistry in young C57BL/6 mice intraperitoneally administrated with vehicle or DBP (10 or 50 mg/kg) for 2 weeks. DBP administered mice were found to have significantly fewer newly generated neurons in hippocampi, and the Morris water maze test revealed that DBP (50 mg/kg) impaired spatial learning and memory. Taken together, these findings suggest that DBP has harmful effects on NPCs and hippocampal neurogenesis and that DBP exposure could lead to learning and memory dysfunctions.

Original languageEnglish
Pages (from-to)239-248
Number of pages10
JournalFood and Chemical Toxicology
Volume129
DOIs
Publication statusPublished - 2019 Jul
Externally publishedYes

Keywords

  • Dibutyl phthalate
  • Hippocampal neurogenesis
  • Neural progenitor cell
  • Spatial learning and memory

ASJC Scopus subject areas

  • Food Science
  • Toxicology

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  • Cite this

    Lee, W., Cho, J. H., Lee, Y., Lee, S., Kim, D. H., Ha, S., Kondo, Y., Ishigami, A., Chung, H. Y., & Lee, J. (2019). Dibutyl phthalate impairs neural progenitor cell proliferation and hippocampal neurogenesis. Food and Chemical Toxicology, 129, 239-248. https://doi.org/10.1016/j.fct.2019.04.040