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Interleukin 6, circadian activity, mouse, behavior, clock gene, hippocampus
Abstract:
The characteristics of the cycles of activity and rest stand out among
the most intensively investigated aspects of circadian rhythmicity in
humans and experimental animals. Alterations in the circadian patterns
of activity and rest are strongly linked to cognitive and emotional
dysfunctions in severe mental illnesses such as Alzheimer's disease (AD)
and major depression (MDD). The proinflammatory cytokine interleukin 6
(IL-6) has been prominently associated with the pathogenesis of AD and
MDD. However, the potential involvement of IL-6 in the modulation of the
diurnal rhythms of activity and rest has not been investigated. Here, we
set out to study the role of IL-6 in circadian rhythmicity through the
characterization of patterns of behavioral locomotor activity in IL-6
knockout (IL-6 KO) mice and wild-type littermate controls. Deletion of
IL-6 did not alter the length of the circadian period or the amount of
locomotor activity under either light-entrained or free-running
conditions. IL-6 KO mice also presented a normal phase shift in response
to light exposure at night. However, the temporal architecture of the
behavioral rhythmicity throughout the day, as characterized by the
quantity of ultradian activity bouts, was significantly impaired under
light-entrained and free-running conditions in IL-6 KO. Moreover, the
assessment of clock gene expression in the hippocampus, a brain region
involved in AD and depression, revealed altered levels of cry1, dec2,
and rev-erb-beta in IL-6 KO mice. These data propose that IL-6
participates in the regulation of ultradian activity/rest rhythmicity
and clock gene expression in the mammalian brain. Furthermore, we
propose IL-6-dependent circadian misalignment as a common pathogenetic
principle in some neurodegenerative and neuropsychiatric disorders.
