title: Impact of traumatic brain injury on sleep structure, electrocorticographic activity and transcriptome in mice.
abstract: Traumatic brain injury (TBI), including mild TBI (mTBI), is importantly associated with vigilance and sleep complaints. Because sleep is required for learning, plasticity and recovery, we here evaluated the bidirectional relationship between mTBI and sleep with two specific objectives: (1) Test that mTBI rapidly impairs sleep-wake architecture and the dynamics of the electrophysiological marker of sleep homeostasis (i.e., non-rapid eye movement sleep delta (1-4Hz) activity); (2) evaluate the impact of sleep loss following mTBI on the expression of plasticity markers that have been linked to sleep homeostasis and on genome-wide gene expression. A closed-head injury model was used to perform a 48h electrocorticographic (ECoG) recording in mice submitted to mTBI or Sham surgery. mTBI was found to immediately decrease the capacity to sustain long bouts of wakefulness as well as the amplitude of the time course of ECoG delta activity during wakefulness. Significant changes in ECoG spectral activity during wakefulness, non-rapid eye movement and rapid eye movement sleep were observed mainly on the second recorded day. A second experiment was performed to measure gene expression in the cerebral cortex and hippocampus after a mTBI followed either by two consecutive days of 6h sleep deprivation (SD) or of undisturbed behavior (quantitative PCR and next-generation sequencing). mTBI modified the expression of genes involved in immunity, inflammation and glial function (e.g., chemokines, glial markers) and SD changed that of genes linked to circadian rhythms, synaptic activity/neuronal plasticity, neuroprotection and cell death and survival. SD appeared to affect gene expression in the cerebral cortex more importantly after mTBI than Sham surgery including that of the astrocytic marker Gfap, which was proposed as a marker of clinical outcome after TBI. Interestingly, SD impacted the hippocampal expression of the plasticity elements Arc and EfnA3 only after mTBI. Overall, our findings reveal alterations in spectral signature across all vigilance states in the first days after mTBI, and show that sleep loss post-mTBI reprograms the transcriptome in a brain area-specific manner and in a way that could be deleterious to brain recovery.
authors.affiliation: Center for Advanced Research in Sleep Medicine and Research Center, Hôpital du Sacré-Cœur de Montréal, 5400 Gouin West Blvd., Montreal, QC, H4J1C5, Canada; Department of Psychiatry, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montreal, QC, H3C3J7, Canada.
authors.forename: Meriem
authors.initials: M
authors.lastname: Sabir
authors.affiliation: Center for Advanced Research in Sleep Medicine and Research Center, Hôpital du Sacré-Cœur de Montréal, 5400 Gouin West Blvd., Montreal, QC, H4J1C5, Canada; Department of Psychology, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montreal, QC, H3C3J7, Canada.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Gaudreault
authors.affiliation: Center for Advanced Research in Sleep Medicine and Research Center, Hôpital du Sacré-Cœur de Montréal, 5400 Gouin West Blvd., Montreal, QC, H4J1C5, Canada; Department of Neuroscience, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montreal, QC, H3C3J7, Canada.
authors.forename: Marlène
authors.initials: M
authors.lastname: Freyburger
authors.affiliation: Department of Pharmacology & Therapeutics, McGill University, McIntyre Building, 3655 Prom. Sir-William-Osler, Montreal, QC, H3G1Y6, Canada.
authors.forename: Renaud
authors.initials: R
authors.lastname: Massart
authors.affiliation: Bioinformatics, Institut de recherches cliniques de Montréal, Montreal, QC, H2W1R7, Canada.
authors.forename: Alexis
authors.initials: A
authors.lastname: Blanchet-Cohen
authors.affiliation: Center for Advanced Research in Sleep Medicine and Research Center, Hôpital du Sacré-Cœur de Montréal, 5400 Gouin West Blvd., Montreal, QC, H4J1C5, Canada.
authors.forename: Manar
authors.initials: M
authors.lastname: Jaber
authors.affiliation: Center for Advanced Research in Sleep Medicine and Research Center, Hôpital du Sacré-Cœur de Montréal, 5400 Gouin West Blvd., Montreal, QC, H4J1C5, Canada; Department of Psychology, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montreal, QC, H3C3J7, Canada.
authors.forename: Nadia
authors.initials: N
authors.lastname: Gosselin
authors.affiliation: Center for Advanced Research in Sleep Medicine and Research Center, Hôpital du Sacré-Cœur de Montréal, 5400 Gouin West Blvd., Montreal, QC, H4J1C5, Canada; Department of Neuroscience, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montreal, QC, H3C3J7, Canada. Electronic address: valerie.mongrain@umontreal.ca.
authors.forename: Valérie
authors.initials: V
authors.lastname: Mongrain
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D001930:Brain Injuries / Q000378:metabolism / Q000503:physiopathology*; D002940:Circadian Rhythm / Q000502:physiology*; D000069280:Electrocorticography; D008297:Male; D051379:Mice; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000378:metabolism / Q000503:physiopathology; D059467:Transcriptome
keywords: Cerebral cortex; Chemokines; Clock genes; Closed-head injury; EEG spectral analysis; Hippocampus; Plasticity genes; Recovery sleep; Sleep architecture; Transcriptome