Neurotoxic effect of 2,5-hexanedione on neural progenitor cells and hippocampal neurogenesis

Abstract 2,5-Hexanedione (HD), a metabolite of n -hexane, causes central and peripheral neuropathy leading to motor neuron deficits. Although chronic exposure to n -hexane is known to cause gradual sensorimotor neuropathy, there are no reports on the effects of low doses of HD on neurogenesis in the...

Full description

Saved in:

Bibliographic Details
Published in:	Toxicology (Amsterdam) Vol. 260; no. 1; pp. 97 - 103
Main Authors:	Kim, Min-Sun, Park, Hee Ra, Park, Mikyung, Kim, So Jung, Kwon, Mugil, Yu, Byung Pal, Chung, Hae Young, Kim, Hyung Sik, Kwack, Seung Jun, Kang, Tae Seok, Kim, Seung Hee, Lee, Jaewon
Format:	Journal Article
Language:	English
Published:	Kidlington Elsevier Ireland Ltd 16-06-2009 Elsevier
Subjects:	2,5-Hexanedione Animals Biological and medical sciences Cell Growth Processes - drug effects Cell Line Cell Survival - drug effects Chemical and industrial products toxicology. Toxic occupational diseases Emergency Hexanones - toxicity Hippocampal neurogenesis Hippocampus - cytology Hippocampus - drug effects Hippocampus - metabolism Immunohistochemistry Lactic Acid - metabolism Male Medical sciences Mice Mice, Inbred ICR Neural progenitor cells Neurogenesis - drug effects Neurogenesis - physiology Neurons - cytology Neurons - drug effects Neurons - metabolism Oxidative Stress - drug effects Random Allocation Reactive Oxygen Species - metabolism Solvents Stem Cells - cytology Stem Cells - drug effects Stem Cells - metabolism Toxicology NPC 2,5-hexanedione ROS reactive oxygen species SGZ CNS central nerve system subgranular zone Hippocampal neurogenesis HD neural progenitor cells Neural progenitor cells 2,5-Hexanedione Organic solvent Toxicity Stem cell Central nervous system Nervous system Neurogenesis Hippocampus Encephalon Progenitor cell
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Abstract 2,5-Hexanedione (HD), a metabolite of n -hexane, causes central and peripheral neuropathy leading to motor neuron deficits. Although chronic exposure to n -hexane is known to cause gradual sensorimotor neuropathy, there are no reports on the effects of low doses of HD on neurogenesis in the central nervous system. In the current study, we explored HD toxicity in murine neural progenitor cells (NPC), primary neuronal culture and young adult mice. HD (500 nM∼50 μM) dose-dependently suppressed NPC proliferation and cell viability, and also increased the production of reactive oxygen species (ROS). HD (10 or 50 mg/kg for 2 weeks) inhibited hippocampal neuronal and NPC proliferation in 6-week-old male ICR mice, as measured by BrdU incorporation in the dentate gyrus, indicating HD impaired hippocampal neurogenesis. In addition, elevated microglial activation was observed in the hippocampal CA3 region and lateral ventricles of HD-treated mice. Lastly, HD dose-dependently decreased the viability of primary cultured neurons. Based on biochemical and histochemical evidence from both cell culture and HD-treated animals, the neurotoxic mechanisms by which HD inhibits NPC proliferation and hippocampal neurogenesis may relate to its ability to elicit an increased generation of deleterious ROS.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0300-483X 1879-3185
DOI:	10.1016/j.tox.2009.03.013