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BubR1 Insufficiency Impairs Affective Behavior and Memory Function in Mice
Chang Hoon Cho1, Zhongxi Yang1,2, Ki Hyun Yoo1
1Department of Neurologic Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA.
International Neurourology Journal
|November 7, 2018
Summary
Reduced levels of the protein budding uninhibited by benzimidazole-related 1 (BubR1) in mice lead to increased anxiety, depression, and memory deficits. This suggests BubR1 is crucial for maintaining normal brain function and may contribute to age-related cognitive decline.
Area of Science:
- Neuroscience
- Molecular Biology
- Aging Research
Background:
- Aging is associated with cognitive decline, but the underlying molecular mechanisms are not fully understood.
- Budding uninhibited by benzimidazole-related 1 (BubR1), a spindle checkpoint kinase, is implicated in age-related pathologies in various tissues, including the brain.
- The specific impact of BubR1 on neurobehavioral functions has not been previously investigated.
Purpose of the Study:
- To investigate the role of BubR1 in regulating behavioral functions.
- To explore the neurobiological functions of BubR1 in vivo.
Main Methods:
- Utilized transgenic mice with hypomorphic BubR1 alleles (BubR1H/H) and mice with targeted BubR1 knockdown in the adult dentate gyrus.
- Assessed anxiety-like behavior using the elevated plus maze and light-dark test.
- Evaluated depression-like behavior with the tail-suspension and forced-swim tests.
- Tested memory function through novel object recognition.
Main Results:
- BubR1H/H mice exhibited increased anxiety, depression-like behavior, and impaired memory compared to wild-type littermates.
- Knockdown of BubR1 in the adult dentate gyrus replicated these behavioral deficits, including increased anxiety, depression-like behavior, and memory impairment.
- These findings indicate a direct link between BubR1 levels and specific behavioral outcomes.
Conclusions:
- BubR1 is essential for maintaining normal affective and memory-related behavioral functions.
- A decline in BubR1 levels with age may significantly contribute to age-related hippocampal dysfunction.
- This study highlights BubR1 as a potential therapeutic target for age-related cognitive and affective disorders.
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