BubR1 Insufficiency Impairs Affective Behavior and Memory Function in Mice.
- Author:
Chang Hoon CHO
1
;
Zhongxi YANG
;
Ki Hyun YOO
;
Alfredo OLIVEROS
;
Mi Hyeon JANG
Author Information
- Publication Type:Original Article
- Keywords: BubR1; Aging; Hippocampus; Memory; Emotion
- MeSH: Adult; Aging; Alleles; Animals; Anxiety; Brain; Cognition; Dentate Gyrus; Hindlimb Suspension; Hippocampus; Humans; Memory*; Mice*; Mice, Transgenic; Pathology; Phosphotransferases
- From:International Neurourology Journal 2018;22(Suppl 3):S122-S130
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: Although aging causes functional declines in cognition, the molecular mechanism underlying these declines remains largely unknown. Recently, the spindle checkpoint kinase budding uninhibited by benzimidazole-related 1 (BubR1) has emerged as a key determinant for age-related pathology in various tissues including brain. However, the neurobehavioral impact of BubR1 has not been explored. In this study, we investigated the role of BubR1 in behavioral function. METHODS: To investigate the neurobiological functions of BubR1 in vivo, we utilized transgenic mice harboring BubR1 hypomorphic alleles (BubR1 H/H mice), which produce low amounts of BubR1 protein, as well as mice that have specific knockdown of BubR1 in the adult dentate gyrus. To assess anxiety-like behavior, the above groups were subjected to the elevated plus maze and the light-dark test, in addition to utilizing the tail-suspension and forced-swim test to determine depression-like behavior. We used novel object recognition to test for memory-related function. RESULTS: We found that BubR1 H/H mice display several behavioral deficits when compared to wild-type littermates, including increased anxiety in the elevated-plus maze test, depression-like behavior in the tail suspension test, as well as impaired memory function in the novel object recognition test. Similar to BubR1 H/H mice, knockdown of BubR1 within the adult dentate gyrus led to increased anxiety-like behavior as well as depression-like behavior, and impaired memory function. CONCLUSIONS: Our study demonstrates a requirement of BubR1 in maintaining proper affective and memory-related behavioral function. These results suggest that a decline in BubR1 levels with advanced age may be a crucial contributor to age-related hippocampal dysfunction.
