title: Sodium butyrate, a histone deacetylase Inhibitor, ameliorates SIRT2-induced memory impairment, reduction of cell proliferation, and neuroblast differentiation in the dentate gyrus.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Dae Young
authors: DY
authors: Yoo
authors: Dae Won
authors: DW
authors: Kim
authors: Mi Jin
authors: MJ
authors: Kim
authors: Jung Hoon
authors: JH
authors: Choi
authors: Hyo Young
authors: HY
authors: Jung
authors: Sung Min
authors: SM
authors: Nam
authors: Jong Whi
authors: JW
authors: Kim
authors: Yeo Sung
authors: YS
authors: Yoon
authors: Soo Young
authors: SY
authors: Choi
authors: In Koo
authors: IK
authors: Hwang
mesh_terms: D000818:Animals; D020148:Butyric Acid / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D018891:Dentate Gyrus / Q000187:drug effects* / Q000503:physiopathology; D000089622:Doublecortin Domain Proteins; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000494:pharmacology*; D056565:Sirtuin 2 / Q000378:metabolism*
chemical_list: D000089622:Doublecortin Domain Proteins; D056572:Histone Deacetylase Inhibitors; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D018697:Nootropic Agents; D020148:Butyric Acid; C418743:Sirt2 protein, mouse; D056565:Sirtuin 2
keywords: Dentate gyrus; Histone deacetylation,; Neurogenesis,; Sirtuin 2,; Sodium butyrate,