All these valproic acid effects could exert positive or negative roles on visual cortical SB203580 purchase plasticity. For instance, recent data indicate that inhibition levels in the adult visual cortex might regulate adult ocular dominance plasticity (Harauzov et al., 2010; Southwell et al., 2010). However, the data also showing a recovery of VEP visual acuity with sodium butyrate, which
shares with valproic acid the HDAC inhibitory activity (Tsankova et al., 2007) but has different pharmacological actions, suggest that increased histone acetylation could be the common mechanism mediating the visual acuity recovery induced by valproic acid and sodium butyrate treatments. In keeping with this interpretation, we found a strong increase in histone acetylation in the visual cortex of the valproic acid-treated rats.
A key role for histone acetylation in visual acuity recovery is also in line with a previous study showing that administration of trichostatin, another HDAC inhibitor, in adult mice promoted visual cortical plasticity, reactivating a sensitivity to MD similar to that of juvenile mice (Putignano et al., 2007). Importantly, the results selleck kinase inhibitor in this manuscript indicate that histone acetylation could also be a crucial step in the mechanisms underlying experience-dependent recovery from amblyopia. Histone acetylation exerts its effect on transcription either by physical remodeling of chromatin structure or by further recruitment of signaling complexes that drive or repress transcription (Peterson & Laniel, 2004). Histone acetylation is achieved by a histone acetyl transferase adding an acetyl group to a lysine residue. Conversely, HDACs remove these acetyl
groups and are generally associated with chromatin inactivation. Therefore, HDAC inhibitors induce histone acetylation and promote gene transcription (Li et al., 2007; Graff & Mansuy, 2009). Increasing evidence, obtained by use of DNA microarrays to profile changes in gene expression of cell lines treated with HDAC inhibitors, demonstrate that the effect of HDAC activity on gene expression is not global because only 1–7% of genes show altered expression (Marks et al., 2000; Glaser et al., 2003), and similar results have also been reported in in vivo studies (Fass et al., 2003; Weaver et al., 2006; Vecsey et al., 2007; Shafaati et al., 2009). In particular, histone acetylation seems to be Selleck Baf-A1 important for the activation of CREB-regulated genes; indeed CREB activation of gene transcription involves CREB-binding protein, a histone acetyltansferase important for activity-regulated gene expression and synaptic plasticity (Mayr & Montminy, 2001; Vo & Goodman, 2001; Alarcon et al., 2004; Korzus et al., 2004). CREB-mediated gene expression is strongly regulated by visual experience during the SP (Pham et al., 1999; Cancedda et al., 2003; Putignano et al., 2007); however, in adult animals experience-dependent regulation of CREB-mediated gene transcription is strongly reduced (Pham et al., 1999; Putignano et al.