Exposing lithium?s circadian action

Study shows that lithium regulates circadian gene expression through a nuclear hormone receptor

Melissa Lee Phillips
Feb 16, 2006
Lithium treatment leads to synchronized circadian oscillations in human cells through the orphan nuclear receptor Rev-erba, according to a study in this week's Science. This molecular pathway may underlie lithium's effects on the circadian clock in people with bipolar disorder, a condition associated with aberrant circadian rhythms, according to the authors.It was already established that Rev-erba is part of the circadian clock and that lithium acts on a protein involved in circadian rhythm, glycogen synthase kinase 3b (GSK3b), said Eric Herzog of Washington University in St. Louis, who was not involved in the research. The researchers "link those two stories," Herzog noted, demonstrating "a pretty convincing specific interaction between lithium, GSK3, and circadian genes."In the classic molecular circadian loop in mammals, the transcription factors BMAL1 and CLOCK activate the clock genes Per and Cry, whose proteins feed back into the...