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Published on: March 23, 2011
13-cis-retinoic acid suppresses hippocampal cell division and hippocampal-dependent learning in mice
James Crandall1, Yasuo Sakai, Jinghua Zhang
1E. K. Shriver Center, University of Massachusetts Medical School, Waltham, MA 02452, USA.
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.
Insights
Accutane
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Biology
Background:
- The active component of Accutane, 13-cis-retinoic acid (RA), is known for its teratogenic effects on the developing central nervous system.
- However, its impact on the adult brain, particularly in regions with ongoing neurogenesis, remains largely unexplored.
Purpose of the Study:
- To investigate the effects of a clinical dose of 13-cis-retinoic acid on neurogenesis and cognitive function in the adult mouse brain.
- To determine the sensitivity of adult neurogenic regions to RA exposure.
Main Methods:
- Adult mice were administered a clinical dose (1 mg/kg/day) of 13-cis-retinoic acid.
- Cell proliferation in the hippocampus and subventricular zone was measured.
- Hippocampal neurogenesis was assessed.
- Spatial learning and memory were evaluated using a radial maze task.
Main Results:
- 13-cis-retinoic acid significantly reduced cell proliferation in both the hippocampus and subventricular zone.
- Hippocampal neurogenesis was suppressed by the treatment.
- The drug severely impaired the mice's capacity to learn the spatial radial maze task.
Conclusions:
- Adult brain regions with active cell proliferation, such as the hippocampus and subventricular zone, are highly sensitive to disruption by clinical doses of 13-cis-retinoic acid.
- This suggests potential adverse effects of Accutane on adult brain function and cognition.
