A mathematical model of the circadian gene expression of clock genes in NIH-3T3 mouse fibroblasts

Abstract

Disruption of circadian rhythms is part of the pathophysiology of bipolar disorder. The

mood-stabilizing properties of lithium have been linked to its effects on the circadian

pacemaker, including clock gene expression, with prolongation of various biological

rhythms. The aim of this study was to further examine the molecular effects of lithium

on the peripheral circadian clock in a cellular model system.

 

We serum-shocked NIH-3T3 cells to synchronize their circadian rhythms, before

administration of lithium chloride (20 mM) or sodium chloride (control; 20 mM). Clock

 gene expressions were measured by q-RT-PCR. To approximate our data, we used a

squared sinus function f(t) of the form:

f(t)=l₁+l ₂exp(-l₃t)sin[(p t/p)+f]sin[(p t/p)+f],

where t is time after the serum shock, l₁ the offset, l₂ the amplitude, l₃ the

dampening, p the period, and f the phase.

 

We found that lithium exposure altered both the period lengths and the amplitudes.

These data further support that lithium influences the circadian pacemaker on the gene

expression level. These effects may be relevant for its mood-stabilizing action in bipolar

disorder.

 

¹ Dr. Einar Martens’ Research Group for Biological Psychiatry, Section for Medical

Genetics and Molecular Medicine, Department of Clinical Medicine, University of

Bergen, Norway,

² Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway,

³ Stem Cell Research Group, Department of Pathology, the Gade Institute, Haukeland University Hospital, Bergen, Norway,

⁴ Stavanger University College, School of Science and Technology, Stavanger, Norway.