Differential expression of HDACs and KATs in high and low regeneration capacity neurons during spinal cord regeneration.

After spinal cord injury (SCI) in mammals, injured axons fail to regenerate. By contrast, lampreys recover from complete spinal transection and axons regenerate selectively in their correct paths. Yet the large, identified reticulospinal neurons in the lamprey brain vary greatly in their regenerative abilities - some have high regeneration capacity (probability of regeneration >50%) and others have low regeneration capacity (<30%) - even though they have similar projection paths. The presence of both regenerating and non-regenerating neurons located in the same brain region and projecting to the same axon tracts suggests that differences in their regenerating abilities depend upon factors intrinsic to the neurons. Previous work has suggested that axon regeneration, especially in PNS, could depend on epigenetic mechanisms of histone modifications, such as the acetylation of histone tails. Our data indicated that expression of the enzymes responsible for regulating the acetylation of histone (KATs and HDACs) - KAT2A, KAT5 and P300 and HDAC3 did not change after SCI in either high regeneration capacity or low regeneration capacity neurons. In the present report, we show a novel and unexpected relationship between neuron regeneration abilities and expression of HDAC1. While HDAC1 expression was downregulated in both high and low regeneration capacity neurons 2 and 4weeks after SCI, it was upregulated at 7weeks at almost all RS neurons. However, at 10weeks post-transection only high regeneration capacity neurons displayed elevated HDAC1 mRNA expression and HDAC1 expression was again downregulated in low regeneration capacity neurons. Moreover, we show that HDAC1 is preferentially expressed in regenerated neurons, but not in non-regenerating neurons. Together, these results suggest that SCI causes significant changes in HDAC1 expression and that HDAC1 expression in regenerating neurons may modulates a survival or regeneration programs.