Bubr1 insufficiency impairs affective behavior and memory function in mice

Chang Hoon Cho, Zhongxi Yang, Ki Hyun Yoo, Alfredo Oliveros, Mi-Hyeon D Jang

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 (BubR1H/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 BubR1H/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 BubR1H/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.

Original languageEnglish (US)
Pages (from-to)S122-S130
JournalInternational Neurourology Journal
Volume22
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

Fingerprint

Hindlimb Suspension
Anxiety
Dentate Gyrus
Depression
benzimidazole
Cognition
Transgenic Mice
Phosphotransferases
Alleles
Pathology
Light
Brain
Proteins
Recognition (Psychology)

Keywords

  • Aging
  • BubR1
  • Emotion
  • Hippocampus
  • Memory

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Urology

Cite this

Bubr1 insufficiency impairs affective behavior and memory function in mice. / Cho, Chang Hoon; Yang, Zhongxi; Yoo, Ki Hyun; Oliveros, Alfredo; Jang, Mi-Hyeon D.

In: International Neurourology Journal, Vol. 22, 01.01.2018, p. S122-S130.

Research output: Contribution to journalArticle

Cho, Chang Hoon ; Yang, Zhongxi ; Yoo, Ki Hyun ; Oliveros, Alfredo ; Jang, Mi-Hyeon D. / Bubr1 insufficiency impairs affective behavior and memory function in mice. In: International Neurourology Journal. 2018 ; Vol. 22. pp. S122-S130.
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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 (BubR1H/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 BubR1H/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 BubR1H/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.",
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