title: Sirtuin-2 inhibition affects hippocampal functions and sodium butyrate ameliorates the reduction in novel object memory, cell proliferation, and neuroblast differentiation.
abstract: We investigated the effects of the sirtuin-2 (SIRT2) inhibitor AK-7 on novel object memory, cell proliferation, and neuroblast differentiation in the dentate gyrus. In addition, we also observed the relationships with sodium butyrate, a histone deacetylase inhibitor, on the hippocampal functions. To investigate the effects of AK-7 on hippocampal functions, 10-week-old C57BL/6 mice were daily injected intraperitoneally with 20 mg/kg AK-7 alone or in combination with subcutaneous administration of 300 mg/kg sodium butyrate, a histone deacetylase inhibitor, for 21 days. A novel object recognition test was conducted on days 20 (training) and 21 (testing) of treatment. Thereafter, the animals were sacrificed for immunohistochemistry for Ki67 (cell proliferation) and doublecortin (DCX, neuroblast differentiation). AK-7 administration significantly reduced the time spent exploring new objects, while treatment in combination with sodium butyrate significantly alleviated this reduction. Additionally, AK-7 administration significantly reduced the number of Ki67-positive cells and DCX-immunoreactive neuroblasts in the dentate gyrus, while the treatment in combination with sodium butyrate ameliorated these changes. This result suggests that the reduction of SIRT2 may be closely related to age-related phenotypes including novel object memory, as well as cell proliferation and neuroblast differentiation in the dentate gyrus. In addition, sodium butyrate reverses SIRT2-related age phenotypes.
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, Korea.
authors.forename: Hyo Young
authors.initials: HY
authors.lastname: Jung
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, Korea.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Yoo
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, Korea.
authors.forename: Jong Whi
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung, Korea.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Anatomy, College of Veterinary Medicine, Kangwon National University, Chuncheon, Korea.
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Veterinary Internal Medicine and Geriatrics, College of Veterinary Medicine, Kangwon National University, Chuncheon, Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Chung
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Korea.
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, Korea.
authors.forename: Yeo Sung
authors.initials: YS
authors.lastname: Yoon
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, Korea.
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
keywords: AK-7; neurogenesis; novel object recognition test; sirtuin 2; sodium butyrate