Abstract
The circadian clock in the suprachiasmatic nucleus (SCN) regulates daily rhythms in physiology and behaviour and is an important part of the mammalian homeostatic system. Previously, we have shown that systemic inflammatory stimulation with lipopolysaccharide (LPS) induced the daytime-dependent phosphorylation of STAT3 in the SCN. Here, we demonstrate the LPS-induced Stat3 mRNA expression in the SCN and show also the circadian rhythm in Stat3 expression in the SCN, with high levels during the day. Moreover, we examined the effects of LPS (1mg/kg), applied either during the day or the night, on the rhythm in locomotor activity of male Wistar rats. We observed that recovery of normal locomotor activity patterns took longer when the animals were injected during the night. The clock genes Per1, Per2 and Nr1d1, and phosphorylation of kinases ERK1/2 and GSK3β are sensitive to external cues and function as the molecular entry for external signals into the circadian clockwork. We also studied the immediate changes in these clock genes expressions and the phosphorylation of ERK1/2 and GSK3β in the suprachiasmatic nucleus in response to daytime or night-time inflammatory stimulation. We revealed mild and transient changes with respect to the controls. Our data stress the role of STAT3 in the circadian clock response to the LPS and provide further evidence of the interaction between the circadian clock and immune system.
Highlights
The temporal organisation of behavioural and physiological functions in mammals mostly depends on the timing signals generated by the circadian clock in the suprachiasmatic nucleus (SCN)
The recovery of locomotor activity from systemic LPS depends on the time of its administration To monitor the recovery from acute infection in natural conditions, we measured the locomotor activity of rats for eight consecutive LD cycles following the systemic LPS administration on LD 0 (Fig 1)
The present study shows that the time of LPS administration affects the recovery rate of locomotor activity rhythm and induces the transient changes in clock gene expression and the levels of phosphorylated forms of ERK1/2 (pERK1/2) and pGSK3β in the rat SCN that may be a part of the steady-state function of the clock in mild pathological conditions
Summary
The temporal organisation of behavioural and physiological functions in mammals mostly depends on the timing signals generated by the circadian clock in the suprachiasmatic nucleus (SCN). The SCN integrates external timing cues with an endogenous molecular clockwork and synchronises circadian oscillations in other brain parts and peripheral tissues [1]. The morphology of the SCN varies across species, but its basic structure is shared by all mammals. It consists of two main parts: the shell or the dorsomedial part (dmSCN), which contains. The day/night difference in the rat SCN response to acute lipopolysaccharide and the rhythmic Stat expression role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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