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Fig. 5.1
Coupled circadian neurons at the hypothalamus and synchronization of circadian oscilla-
tors in peripheral organs
circadian oscillators are controlled by the circadian neurons through messages
sent by the latter, in the form of hormones (ACTH, cortisol, etc.), metabolites,
inputs from the sympathetic neural system, or variations in body temperature
[
61
,
67
,
68
,
104
] (see Fig.
5.1
). Circadian rhythms affect cell cycle apoptosis and
DNA repair, drug metabolism, and detoxification, as well as angiogenesis. The
disruption of periodicity and synchronism in circadian oscillators is known to be
responsible for the appearance of malignancies [
32
,
33
,
105
,
106
]. On the other hand,
pharmacological treatment of tumors when taking into account the variations of
proteins concentration controlled by the circadian oscillators can be more efficient.
Mathematical models of circadian oscillators consist of sets of ordinary differential
equations describing the feedback loop of the generation of proteins in the circadian
cells. The main stages of these feedback loops are transcription of genes into mRNA,
translation of mRNA into proteins, and inhibition of the transcription stage by the
generated protein. The number of ordinary differential equations in such models is
moderate in simple organisms (e.g., neurospora and drosophila) whereas it becomes
elevated in the case of mammals. In this chapter the model of the neurospora
circadian oscillators will be considered for testing the method of feedback control
and synchronization of the circadian cells. However, the method is generic and can
be applied to more elaborated and increased order models of circadian oscillators.
