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  • Title: Sodium butyrate, a histone deacetylase Inhibitor, ameliorates SIRT2-induced memory impairment, reduction of cell proliferation, and neuroblast differentiation in the dentate gyrus.
    Author: Yoo DY, Kim DW, Kim MJ, Choi JH, Jung HY, Nam SM, Kim JW, Yoon YS, Choi SY, Hwang IK.
    Journal: Neurol Res; 2015 Jan; 37(1):69-76. PubMed ID: 24963697.
    Abstract:
    OBJECTIVES: Histone deacetylases (HDACs) play a key role in synaptic plasticity and learning and memory. Sirtuin 2 (SIRT2), a class III HDAC, is abundantly expressed in neurons and functions as a mitotic exit regulator in dividing cells. In this study, we investigated the role of SIRT2 in cell proliferation and neuroblast differentiation in the mouse dentate gyrus. METHODS: To facilitate the delivery of SIRT2 into neurons, we constructed a PEP-1-SIRT2 fusion protein. Mice were divided into three groups: vehicle (PEP-1), SIRT2, and SIRT2 with sodium butyrate (an HDAC inhibitor). PEP-1 or PEP-1-SIRT2 fusion protein was administered intraperitoneally to 7-week-old mice once a day for 3 weeks, and the mice were killed 2 h after the last administration. Sodium butyrate, an HDAC inhibitor, was subcutaneously administered in parallel with PEP-1-SIRT2 once a day for 3 weeks. RESULTS: The administration of PEP-1-SIRT2 alone significantly reduced the time spent exploring a new object in the novel object recognition test, whereas treatment with sodium butyrate increased the time spent exploring a new object. RESULTS of Ki67 and doublecortin immunohistochemistry revealed that the administration of PEP-1-SIRT2 significantly reduced cell proliferation and neuroblast differentiation, respectively, in the dentate gyrus. However, the administration of sodium butyrate significantly ameliorated the SIRT2-induced reduction in cell proliferation and neuroblast differentiation. CONCLUSION: This result suggests that histone acetylation and deacetylation are key factors modulating hippocampal functions such as memory formation, cell proliferation, and neuroblast differentiation in the dentate gyrus.
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