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...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 101; no. 14; pp. 5111 - 5116
Main Authors Crandall, James, Sakai, Yasuo, Zhang, Jinghua, Koul, Omanand, Mineur, Yann, Crusio, Wim E., McCaffery, Peter, Dowling, John E.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 06.04.2004
National Acad Sciences
Subjects
Animals
Biological Sciences
Blood plasma
Brain
Brain research
Cell division
Cell Division - drug effects
Cell growth
Hippocampus
Hippocampus - cytology
Hippocampus - drug effects
Hippocampus - physiology
Immunohistochemistry
Isotretinoin - blood
Isotretinoin - pharmacology
Learning
Maze Learning - physiology
Mazes
Mice
Neurogenesis
Neurology
Neurons
Neuroscience
Pharmaceuticals
Receptors
Receptors, Retinoic Acid - metabolism
Rodents
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Summary: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 in 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.
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This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: RA, retinoic acid; SGZ, subgranular zone; SVZ, subventricular zone; RAR, RA receptor.
Edited by John E. Dowling, Harvard University, Cambridge, MA, and approved January 21, 2004
To whom correspondence should be addressed. E-mail: peter.mccaffery@umassmed.edu.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0306336101