The Regulatory Effect Of Histone Acetylation On Neurodegenerative Disease By Using PS1/PS2Double Knockout Mice

Alzheimer’s disease (AD) is the most common central nervous system degenerative disease which is mainly exhibited as the progressive cognitive impairment and memory deficit. Using forebrain conditioned presenilin1and presenilin2double knockout mice (cDKO), we studied the long term effect of histone deacetylase inhibitor sodium butyrate on the memory performance of cDKO mice as well as on the neurogenesis.In our previous study, it has been demonstrated that continuous administration of sodium butyrate for21days rescued both memory deficit as well as forebrain degenerative phenotypes. To investigate the underling mechanisms, we studied the effect of sodium butyrate on adult neurogenesis. We found that indeed sodium butyrate significantly increased neurogenesis in hippocampal DG area of cDKO mice. However, the effects of sodium butyrate on both memory performance and neurogenesis turned out to be transient. After21-day drug treatment, the memory performance was tested one month later. Different from our previous data which showed rescue effect immediately after drug treatment, we found that cDKO mice showed no significant memory improvement compared with no treatment control. Furthermore, there was no significant difference of the neurogenesis in hippocampal DG area. These results indicate that although histone deacetylase can be served as a potential target for treating AD, continuous drug administration may be required.