13-cis-retinoic acid suppresses hippocampal cell division and hippocampal-dependent learning in mice

James Crandall, Yasuo Sakai, Jinghua Zhang, Omanand Koul, Yann Mineur, Wim E Crusio, Peter McCaffery

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172 Citations (Scopus)

Abstract

The active component of the acne drug Accutane is 13-cis-retinoic acid (RA), and it is highly teratogenic for the developing central nervous system. Very little is known, however, regarding the effect of this drug on the adult brain. Regions of the brain that may be susceptible to RA are those that continue to generate new neurons. In the adult mouse, neurogenesis is maintained in the hippocampus and subventricular zone. This report demonstrates that a clinical dose (1 mg/kg/day) of 13-cis-RA in mice significantly reduces cell proliferation in the hippocampus and the subventricular zone, suppresses hippocampal neurogenesis, and severely disrupts capacity to learn a spatial radial maze task. The results demonstrate that the regions of the adult brain where cell proliferation is ongoing are highly sensitive to disruption by a clinical dose of 13-cis-RA.
Original languageEnglish
Pages (from-to)5111-5116
Number of pages6
JournalPNAS
Volume101
Issue number14
DOIs
Publication statusPublished - Apr 2004

Keywords

  • Animals
  • Cell Division
  • Hippocampus
  • Immunohistochemistry
  • Isotretinoin
  • Maze Learning
  • Mice
  • Receptors, Retinoic Acid

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