| Alzheimer’s disease (AD) is a neurodegenerative disease. The forebrain conditional double knockout mice (cDKO) showed similar neurodegenerative phenotypes as AD patients with a defect in learning and memory as well as forebrain degeneration. In order to uncover the relationship between histone deacetylation level and AD, We injected the histone deacetylase (HDAC) inhibitor sodium butyrate (SB) on cDKO mice and studied the effect of HDAC inhibitor SB on neurodegenerative phenotypes of cDKO mice in the levels of behavior, brain morphology, and biochemistry.After21days by intraperitoneal injection of HDAC inhibitor SB, contextual fear memory in5-month-old cDKO mice has been raised to the level that is no different from the control mice, whereas there is a defect of the memory in cDKO mice without SB treatment. SB has no effect on the amygdala dependent cued fear memory. Besides, HDAC inhibitor SB ameliorates the forebrain degenerative phenotypes and the neural protection of SB can at least last for1month after its withdrawal:an increase in the cortical thickness and a decrease in the lateral ventricle area as well as a gain of synaptic density in CA1Stratum Radiatum have been observed in6-month-old cDKO mice treated by SB compared with cDKO mice without SB treatment. Furthermore, there is a decreasing histone3acetylation level, a rising phosphorylation level of Tau and an overexpression of GFAP in the cortex of cDKO mice compared with the control mice. However, histone3acetylation level and Tau phosphorylation level have been increased and decreased individually in the cortex of cDKO mice treated by SB compared with the ones without SB treatment. All these results show that the deficiencies of histone acetylation level may serve as an important factor in contributing AD.This study, as a preliminary research study, may help us further reveal the regulatory role of histone acetylation in long-term memory, uncover the epigenetic related molecular mechanisms in alleviating neurodegenerative diseases, and ultimately find potential drug targets for treating AD. |
