13-cis-retinoic acid suppresses hippocampal cell division and hippocampal-dependent learning in mice.
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.
Crandall
James
J
E. K. Shriver Center, University of Massachusetts Medical School, Waltham, MA 02452, USA.
Sakai
Yasuo
Y
Zhang
Jinghua
J
Koul
Omanand
O
Mineur
Yann
Y
Crusio
Wim E
WE
McCaffery
Peter
P
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D007150:Immunohistochemistry; D015474:Isotretinoin / Q000097:blood / Q000494:pharmacology*; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D018168:Receptors, Retinoic Acid / Q000378:metabolism
D018168:Receptors, Retinoic Acid; D015474:Isotretinoin