Mitogen-activated protein kinase is a functional component of the autonomous circadian system in the suprachiasmatic nucleus.
The suprachiasmatic nucleus (SCN) is the master circadian pacemaker driving behavioral and physiological rhythms in mammals. Circadian activation of mitogen-activated protein kinase [MAPK; also known as ERK (extracellular signal-regulated kinase)] is observed in vivo in the SCN under constant darkness, although the biological significance of this remains unclear. To elucidate this question, we first examined whether MAPK was autonomously activated in ex vivo SCN slices. Moreover, we investigated the effect of MAPK inhibition on circadian clock gene expression and neuronal firing rhythms using SCN-slice culture systems. We show herein that MAPK is autonomously activated in the SCN, and our data demonstrate that inhibition of the MAPK activity results in dampened rhythms and reduced basal levels in circadian clock gene expression at the SCN single-neuron level. Furthermore, MAPK inhibition attenuates autonomous circadian neuronal firing rhythms in the SCN. Thus, our data suggest that light-independent MAPK activity contributes to the robustness of the SCN autonomous circadian system.
Akashi
Makoto
M
Department of Vascular Failure Research, Faculty of Medicine, Saga University, Saga 849-8501, Japan. akashima@med.saga-u.ac.jp
Hayasaka
Naoto
N
Yamazaki
Shin
S
Node
Koichi
K
D056930:ARNTL Transcription Factors; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002070:Butadienes / Q000494:pharmacology; D002940:Circadian Rhythm / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D049449:Luminescence; D020935:MAP Kinase Signaling System; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009570:Nitriles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000201:enzymology*
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D002070:Butadienes; D004791:Enzyme Inhibitors; D020928:Mitogen-Activated Protein Kinases; D009570:Nitriles; C538961:Bmal1 protein, mouse; C113580:U 0126