1. ERK signaling pathway regulates sleep duration through activity-induced gene expression during wakefulness
- Author
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Cyril Mikhail, Sonia Jimenez, Mehdi Tafti, and Angélique Vaucher
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,medicine.medical_specialty ,Time Factors ,MAP Kinase Signaling System ,Blotting, Western ,Gene Expression ,Mice, Transgenic ,Nerve Tissue Proteins ,Biology ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Homer Scaffolding Proteins ,Internal medicine ,medicine ,Animals ,Premovement neuronal activity ,Phosphorylation ,Wakefulness ,Molecular Biology ,Neuroscience of sleep ,Cells, Cultured ,Mice, Knockout ,Mitogen-Activated Protein Kinase 1 ,Regulation of gene expression ,Neurotransmitter Agents ,Mitogen-Activated Protein Kinase 3 ,Reverse Transcriptase Polymerase Chain Reaction ,Cell Biology ,Cytoskeletal Proteins/genetics ,Cytoskeletal Proteins/metabolism ,DNA-Binding Proteins/genetics ,DNA-Binding Proteins/metabolism ,Gene Expression/drug effects ,Gene Expression/genetics ,Homer Scaffolding Proteins/genetics ,Homer Scaffolding Proteins/metabolism ,MAP Kinase Signaling System/drug effects ,MAP Kinase Signaling System/genetics ,Mice, Inbred C57BL ,Mitogen-Activated Protein Kinase 1/genetics ,Mitogen-Activated Protein Kinase 1/metabolism ,Mitogen-Activated Protein Kinase 3/genetics ,Mitogen-Activated Protein Kinase 3/metabolism ,Nerve Tissue Proteins/genetics ,Nerve Tissue Proteins/metabolism ,Neurotransmitter Agents/pharmacology ,Sleep/genetics ,Sleep Deprivation ,Transcription Factors/genetics ,Transcription Factors/metabolism ,Wakefulness/genetics ,Cell biology ,DNA-Binding Proteins ,Cytoskeletal Proteins ,Sleep deprivation ,030104 developmental biology ,Endocrinology ,Synaptic plasticity ,Signal transduction ,medicine.symptom ,Sleep ,030217 neurology & neurosurgery ,Transcription Factors - Abstract
Wakefulness is accompanied by experience-dependent synaptic plasticity and an increase in activity-regulated gene transcription. Wake-induced genes are certainly markers of neuronal activity and may also directly regulate the duration of and need for sleep. We stimulated murine cortical cultures with the neuromodulatory signals that are known to control wakefulness in the brain and found that norepinephrine alone or a mixture of these neuromodulators induced activity-regulated gene transcription. Pharmacological inhibition of the various signaling pathways involved in the regulation of gene expression indicated that the extracellular signal-regulated kinase (ERK) pathway is the principal one mediating the effects of waking neuromodulators on gene expression. In mice, ERK phosphorylation in the cortex increased and decreased with wakefulness and sleep. Whole-body or cortical neuron-specific deletion of Erk1 or Erk2 significantly increased the duration of wakefulness in mice, and pharmacological inhibition of ERK phosphorylation decreased sleep duration and increased the duration of wakefulness bouts. Thus, this signaling pathway, which is highly conserved from Drosophila to mammals, is a key pathway that links waking experience-induced neuronal gene expression to sleep duration and quality.
- Published
- 2017