13-cis Retinoic acid (accutane) suppresses hippocampal cell survival in mice.
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.
Sakai
Yasuo
Y
UMMS/E.K. Shriver Center, 200 Trapelo Rd., Waltham, MA 02452, USA.
Crandall
James E
JE
Brodsky
Jacob
J
McCaffery
Peter
P
D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002470:Cell Survival / Q000187:drug effects*; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D015474:Isotretinoin / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D050697:Retinal Dehydrogenase; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology
D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D000445:Aldehyde Oxidoreductases; D050697:Retinal Dehydrogenase; D015474:Isotretinoin; D001973:Bromodeoxyuridine