Dibutyl phthalate impairs neural progenitor cell proliferation and hippocampal neurogenesis

Food Chem Toxicol. 2019 Jul;129:239-248. doi: 10.1016/j.fct.2019.04.040. Epub 2019 Apr 25.

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.

Keywords: Dibutyl phthalate; Hippocampal neurogenesis; Neural progenitor cell; Spatial learning and memory.

MeSH terms

  • Animals
  • Cell Cycle Checkpoints / drug effects
  • Cell Line
  • Cell Proliferation / drug effects*
  • Dibutyl Phthalate / toxicity*
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Learning / drug effects
  • Male
  • Memory / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / drug effects*
  • Neurogenesis / drug effects*
  • Oxidative Stress / drug effects
  • Plasticizers / toxicity*
  • Reactive Oxygen Species / metabolism

Substances

  • Plasticizers
  • Reactive Oxygen Species
  • Dibutyl Phthalate