de Menezes Mayara Ferraz, Nicola Fabrício, Vital da Silva Ivy Reichert, Vizuete Adriana, Elsner Viviane Rostirola, Xavier Léder Leal, Gonçalves Carlos Alberto Saraiva, Netto Carlos Alexandre, Mestriner Régis Gemerasca
Neurorehabilitation and Neural Repair Research Group; Graduate Program in Cellular and Molecular Biology, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Department of Biochemistry, Basic Science Institute, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Neural Regen Res. 2018 Nov;13(11):1945-1952. doi: 10.4103/1673-5374.239443.
Emerging evidence has suggested global histone H4 acetylation status plays an important role in neural plasticity. For instance, the imbalance of this epigenetic marker has been hypothesized as a key factor for the development and progression of several neurological diseases. Likewise, astrocytic reactivity - a well-known process that markedly influences the tissue remodeling after a central nervous system injury - is crucial for tissue remodeling after spinal cord injury (SCI). However, the linkage between the above-mentioned mechanisms after SCI remains poorly understood. We sought to investigate the relation between both glial fibrillary acidic protein (GFAP) and S100 calcium-binding protein B (S100B) (astrocytic reactivity classical markers) and global histone H4 acetylation levels. Sixty-one male Wistar rats (aged ~3 months) were divided into the following groups: sham; 6 hours post-SCI; 24 hours post-SCI; 48 hours post-SCI; 72 hours post-SCI; and 7 days post-SCI. The results suggested that GFAP, but not S100B was associated with global histone H4 acetylation levels. Moreover, global histone H4 acetylation levels exhibited a complex pattern after SCI, encompassing at least three clearly defined phases (first phase: no changes in the 6, 24 and 48 hours post-SCI groups; second phase: increased levels in the 72 hours post-SCI group; and a third phase: return to levels similar to control in the 7 days post-SCI group). Overall, these findings suggest global H4 acetylation levels exhibit distinct patterns of expression during the first week post-SCI, which may be associated with GFAP levels in the perilesional tissue. Current data encourage studies using H4 acetylation as a possible biomarker for tissue remodeling after spinal cord injury.
新出现的证据表明,整体组蛋白H4乙酰化状态在神经可塑性中起重要作用。例如,这种表观遗传标记的失衡被认为是几种神经疾病发生和发展的关键因素。同样,星形胶质细胞反应性——这是一个众所周知的过程,对中枢神经系统损伤后的组织重塑有显著影响——对脊髓损伤(SCI)后的组织重塑至关重要。然而,SCI后上述机制之间的联系仍知之甚少。我们试图研究胶质纤维酸性蛋白(GFAP)和S100钙结合蛋白B(S100B)(星形胶质细胞反应性的经典标记物)与整体组蛋白H4乙酰化水平之间的关系。61只雄性Wistar大鼠(约3个月大)被分为以下几组:假手术组;SCI后6小时;SCI后24小时;SCI后48小时;SCI后72小时;以及SCI后7天。结果表明,GFAP而非S100B与整体组蛋白H4乙酰化水平相关。此外,SCI后整体组蛋白H4乙酰化水平呈现出复杂的模式,至少包括三个明确的阶段(第一阶段:SCI后6、24和48小时组无变化;第二阶段:SCI后72小时组水平升高;第三阶段:SCI后7天组恢复到与对照组相似的水平)。总体而言,这些发现表明,SCI后第一周内整体H4乙酰化水平呈现出不同的表达模式,这可能与损伤周围组织中的GFAP水平有关。目前的数据鼓励开展研究,将H4乙酰化作为脊髓损伤后组织重塑的一种可能的生物标志物。