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.