Identification of intellectual disability genes showing circadian clock-dependent expression in the mouse hippocampus.
Sleep is strongly implicated in learning, especially in the reprocessing of recently acquired memory. Children with intellectual disability (ID) tend to have sleep-wake disturbances, which may contribute to the pathophysiology of the disease. Given that sleep is partly controlled by the circadian clock, we decided to study the rhythmic expression of genes in the hippocampus, a brain structure which plays a key role in memory in humans and rodents. By investigating the hippocampal transcriptome of adult mice, we identified 663 circadian clock controlled (CCC) genes, which we divided into four categories based on their temporal pattern of expression. In addition to the standard core clock genes, enrichment analysis identified several transcription factors among these hippocampal CCC genes, and our findings suggest that genes from one cluster regulate the expression of those in another. Interestingly, these hippocampal CCC genes were highly enriched in sleep/wakefulness-related genes. We show here that several genes in the glucocorticoid signaling pathway, which is involved in memory, show a CCC pattern of expression. However, ID genes were not enriched among these CCC genes, suggesting that sleep or learning and memory disturbances observed in patients with ID are probably not related to the circadian clock in the hippocampus.
Institut National de la Santé et de la Recherche Médicale (INSERM), U1016, Institut Cochin, Paris, France; Université Paris Descartes Paris V, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique (CNRS), UMR8104, Institut Cochin, Paris, France.
J
J
Renaud
Institut National de la Santé et de la Recherche Médicale (INSERM), U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique (CNRS), UMR8104, Institut Cochin, Paris, France.
F
F
Dumont
Centre National de la Recherche Scientifique (CNRS), UMR, INCI, Strasbourg, France.
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M
Khelfaoui
Centre National de la Recherche Scientifique (CNRS), UMR, INCI, Strasbourg, France.
S R
SR
Foisset
Institut National de la Santé et de la Recherche Médicale (INSERM), U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique (CNRS), UMR8104, Institut Cochin, Paris, France.
F
F
Letourneur
Institut National de la Santé et de la Recherche Médicale (INSERM), U1016, Institut Cochin, Paris, France; Université Paris Descartes Paris V, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique (CNRS), UMR8104, Institut Cochin, Paris, France.
T
T
Bienvenu
Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
O
O
Khwaja
Institut National de la Santé et de la Recherche Médicale (INSERM), U1016, Institut Cochin, Paris, France; Université Paris Descartes Paris V, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique (CNRS), UMR8104, Institut Cochin, Paris, France.
O
O
Dorseuil
Institut National de la Santé et de la Recherche Médicale (INSERM), U1016, Institut Cochin, Paris, France; Université Paris Descartes Paris V, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique (CNRS), UMR8104, Institut Cochin, Paris, France. Electronic address: pierre.billuart@inserm.fr.
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P
Billuart
D000818:Animals; D015153:Blotting, Western; D057906:Circadian Clocks / Q000235:genetics* / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D008607:Intellectual Disability / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
circadian clock; hippocampus; intellectual disability; memory; sleep