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Sodium butyrate, a histone deacetylase Inhibitor, ameliorates SIRT2-induced memory impairment, reduction of cell proliferation, and neuroblast differentiation in the dentate gyrus.

Neurological research (2014-06-26)
Dae Young Yoo, Dae Won Kim, Mi Jin Kim, Jung Hoon Choi, Hyo Young Jung, Sung Min Nam, Jong Whi Kim, Yeo Sung Yoon, Soo Young Choi, In Koo Hwang
ABSTRACT

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. 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. 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. 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
3,3′-Diaminobenzidine tetrahydrochloride, tablet, 10 mg substrate per tablet
Sigma-Aldrich
Sodium butyrate, ≥98.5% (GC)
Sigma-Aldrich
Sodium butyrate, 98%
SAFC
Sodium butyrate
Supelco
Sodium butyrate, certified reference material, TraceCERT®