Science Update February 17, 2006
Lithium Blocks Enzyme To Help Cells’ Clocks Keep On Tickin’
A master clock in the brain, reset by light, enforces a daily rhythm within every cell that mirrors the organism's activity cycles, such as sleep, body temperature and metabolism. For this intracellular clock to work properly, clock genes must turn on and off in synchronized, rhythmic feedback loops — a process likely upset in bipolar disorder.
In cultured cells, Klein and colleagues showed that lithium triggers a critical step in synchronizing the rhythmic expression of the clock genes. Lithium turned off the enzyme GSK-3ß, causing the receptor Rev-erbα to degrade, leading to the rhythmic turning-on of the protein Bmal1, which starts the clock cycle. The results reveal a pathway by which lithium may act to restore daily rhythms in bipolar disorder.
A version of the GSK-3ß gene has been linked to a milder, more easily treatable form of bipolar disorder. Valproic acid, another mood stabilizer used to treat bipolar disorder, has also been found to modulate daily rhythms. The researchers suggest that "targeting Rev-erbα degradation may have potential in the treatment of bipolar and circadian disorders."
Yin l, Wang J, Klein PS, Lazar MA, Nuclear receptor rev-erbα is a critical lithium-sensitive component of the circadian clock. Science, Vol. 311. no. 5763, pp. 1002 - 1005.
NIMH Press Office
- Mental Health Information
- Statistics on Mental Disorders
- Summaries of Scientific Meetings
- Information about NIMH
- RePORTER: Research Portfolio Online Reporting Tool Expenditures and Results
- PubMed Central: An Archive of Life Sciences Journals
- Recommendations for Reporting on Suicide
- News from the FieldExternal Link: Please review our disclaimer.
News From the Field
NIMH-Funded Science on EurekAlert
- Out of Sync With the World: Body Clocks of Depressed People Are Altered at Cell LevelExternal Link: Please review our disclaimer.
- Nerve Stimulation for Severe Depression Changes Brain FunctionExternal Link: Please review our disclaimer.
- Nearly 20 Percent of Suicidal Youths Have Guns in Their HomeExternal Link: Please review our disclaimer.