Identification of intellectual disability genes showing circadian clock-dependent expression in the mouse hippocampus. (12th November 2015)

• Record Type: Journal Article
• Authors: Renaud, J.; Dumont, F.; Khelfaoui, M.; Foisset, S.R.; Letourneur, F.; Bienvenu, T.; Khwaja, O.; Dorseuil, O.; Billuart, P.
• Is Part Of: Neuroscience. Volume 308(2015)
• Page Start: 11
• Page End: 50
• Publication Date: 2015-11-12
• Subjects: AA ascorbic acid -- ASD Autism Spectrum Disorders -- CCC circadian clock controlled -- CR circadian rhythm -- CT Circadian Time -- HSPs heat shock proteins -- ID intellectual disability -- IPA Ingenuity Pathway Analysis -- IQ intelligence quotient -- REM rapid eye movement -- SCN suprachiasmatic nucleus -- SWG sleep-wakefulness-related genes -- SWS slow wave sleep -- TF transcription factor -- TFBSs transcription factor binding sites; circadian clock -- hippocampus -- sleep -- memory -- intellectual disability; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2015.08.066
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Identification of 663 circadian clock controlled genes in the hippocampus. Inter-regulation of circadian clock controlled gene expression in the hippocampus. Expression of intellectual disability genes is not preferentially controlled by circadian clock. Identification of 30 intellectual disability genes transcriptionally controlled by circadian clock. Abstract: 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.