13-cis Retinoic acid (accutane) suppresses hippocampal cell survival in mice

Yasuo Sakai, James E Crandall, Jacob Brodsky, Peter McCaffery

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)


Use of the acne drug Accutane (13-cis retinoic acid, [13-cis RA]) has been associated with severe depression. This association has been considered controversial because no causative link has been found between 13-cis RA and this disorder. A recent hypothesis has suggested that atrophy of the hippocampus can result in depression. We now show, in a mouse model, that endogenous RA generated by synthetic enzymes in the meninges acts on hippocampal granule neurons, and chronic (3-week) exposure to a clinical dose of 13-cis RA may result in hippocampal cell loss. In humans this may be conjectured to be the mechanism by which Accutane contributes to depression.
Original languageEnglish
Pages (from-to)436-440
Number of pages5
JournalAnnals of the New York Academy of Sciences
Publication statusPublished - 2004


  • Aldehyde Oxidoreductases
  • Animals
  • Bromodeoxyuridine
  • Cell Count
  • Cell Survival
  • Drug Administration Schedule
  • Gene Expression Regulation
  • Hippocampus
  • Immunohistochemistry
  • Isotretinoin
  • Mice
  • Neurons
  • Receptors, Retinoic Acid
  • Retinal Dehydrogenase
  • Time Factors
  • Tretinoin


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