Impact d'un traumatisme crânio-cérébral léger sur l’architecture du sommeil et le
transcriptome dans un modèle murin
Mild traumatic brain injury (mTBI) is one of the most common neurological disorders affecting public health. Sleep disorders are common in patients with mTBI. Studies in rodents show that some synaptic plasticity markers decreased after mTBI which could impair brain plasticity. We suggest that sleep loss intensifies the negative effect of mTBI, which may reflect changes of synaptic plasticity markers or changes of different physiological pathway that regulates the sleep process. Using a "closed head injury" model, we have studied the bidirectional relationship between mTBI and sleep by investigating the effects of mTBI on sleep structure, and that of sleep deprivation (SD) on gene expression post-mTBI. First, EEG activity was monitored to investigate if sleep architecture is altered following mTBI. We then tested if SD, following mTBI, induces changes in gene expression of plasticity markers (Arc, Homer1a, Hif1a, Bdnf, Fos, and Ephrins), which have also been linked to sleep regulation. We also investigated the effect of SD post-mTBI on genome wide gene expression in target regions. The main results obtained in this study confirm that mTBI affects wakefulness, and significantly changes spectral activity during wakefulness, rapid eye movement (REM) sleep, and non-REM sleep on the second 24 hours post-TCL. Interestingly, the capacity to sustain long bouts of wakefulness was impaired immediately after mTBI. In addition, delta activity time course was altered by mTBI during wakefulness. In parallel to these alterations, changes in gene expression were observed. Only Arc and EfnA3 showed a mTBI/SD interaction in the hippocampus specifically, whereas expression of all other genes seemed to be affected by SD or mTBI independently. Our results indicate for the first time that the TCL induced the expression of two chemokines (Ccl3 and Cxcl5) in the cerebral cortex and hippocampus 2.5 days post-TCL. Also, we observed that the TCL induces a decrease in the expression of Lgals3 and S100A8 in the cortex, and an increase of Olig2 in the hippocampus.Results of SD effects on genome wide gene expression in the cortex and hippocampus show significant changes in genes involved in various physiological functions, such as circadian rhythms, inflammation, and also glial cell activation. In general, our results precise changes in wakefulness as well as in expression of various genes after mTBI.
Trauma EEG Activation gliale Sleep/wake process Synaptic plasticity EEG Glial activation