Glial fibrillary acidic protein levels are associated with global histone H4 acetylation after spinal cord injury in rats

Abstract

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.

Keywords: ELISA-immunoassay; S100 calcium-binding protein B; astrocyte; glial fibrillary acidic protein; histones; neural plasticity; neural repair; rats; recovery; spinal cord injury.

Figure 1

Cavitation area in the spinal cord injury (SCI) model. (A) Sham spinal cord section in rats at thoracic level. (B) Histological image showing a spinal cord injury at T10 level. (C) Cavitation area in the lesion epicenter (n = 18). ***P < 0.001 (one-way analysis of variance followed by the Bonferroni post hoc test).

Figure 2

Global H4 acetylation, glial fibrillary acidic protein and S100 calcium-binding protein B levels at different time points after spinal cord injury (SCI). (A) Global histone H4 acetylation; (B) glial fibrillary acidic protein (GFAP); and (C) S100 calcium-binding protein B (S100B) levels at studied time points. Data are expressed as the mean ± standard error of the mean (SEM) (n = 43). *P < 0.05 and ***P < 0.001 (one-way analysis of variance followed by the Bonferroni post hoc test).