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

研究成果: Article

3 引用 (Scopus)

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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.

元の言語English
ページ(範囲)239-248
ページ数10
ジャーナルFood and Chemical Toxicology
129
DOI
出版物ステータスPublished - 2019 7
外部発表Yes

ASJC Scopus subject areas

  • Food Science
  • Toxicology

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    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