Title : Relationship between spinal cord injury, epigenetic and physical exercise
Abstract:
Emerging evidences have been pointed out that the imbalance of epigenetic machinery exert a pivotal role in the physiopathology of several neurological, neurodegenerative and neuropsychiatric conditions. However, this relationship in spinal cord injury (SCI) have been poorly investigated. Therefore, our research group firstly evaluated the modulation of global histone H4 acetylation levels, an important epigenetic mark, after a thoracic SCI model in rats. Male Wistar rats aged 3 months were submitted to a thoracic SCI model and global histone H4 acetylation levels were measured at different time-points: 6h, 24h, 48h, 72h and 7days after. The Animal Bioethics Committee of both Federal University of Rio Grande do Sul (number 26116) and Pontifical Catholic University of Rio Grande do Sul (number 15/00492) approved the study protocol. It was observed that global histone H4 acetylation levels changed at the evaluated time-groups (P=0.0001). Post hoc tests showed the 72h post-SCI group was significantly increased from all the other groups (P≤0.03). Taken together, our findings suggested that histone H4 acetylation levels might emerge as novel possible biomarker in SCI. These preliminary findings may open new avenues for introducing therapies and strategies in the preventive management and treatment of SCI, regarding therapeutic epigenetic modulation in this devastating and life-changing disease. Thus, based on these findings, and considering that it is widely described in the literature that physical exercise, a non-invasive and easily accessible intervention, is an important epigenetic modulator agent in different populations, we investigated the effect of a single bout of gait training with body weight support (BWS) on global histone H4 acetylation levels in peripheral blood of incomplete SCI adult patients. Interestingly, we also compared this response when training was performed on the floor (walker) or in a treadmill. This study was approved by the Ethics and Research Committee of the Centro Universitário Metodista IPA (1.940.987). No difference was observed in histone H4 global acetylation levels after BWS gait training both when the patients were submitted to the treadmill or to walker sessions. We suggest that chronic interventions must be performed to analyze the long-term effects of physical exercise on epigenetic modulation in SCI, as well the possible involvement of other epigenetic markers such as histone H3 acetylation, DNA methylation and microRNA in this response. Future studies should be done in order to elucidate these questions
