Effects of varying levels and differing durations of calorie restriction on cellular and synaptic proteins, as well as the inflammatory state of the female mouse brain
Author(s)
Advisor
Date
2020-10Publisher
Bilkent University
Language
English
Type
ThesisItem Usage Stats
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Abstract
Aging is an inevitable and complicated process leading to functional decline. Regarding brain aging, cognitive decline takes place in multiple domains, including learning, memory, executive functions, motor coordination, and language. At the
cellular and molecular level, age-related cognitive decline is elucidated with certain hallmarks, including aberrant neuronal network, stem cell exhaustion, glial cell activation, and inflammation. Calorie restriction (CR) is a widely-utilized
approach for coping with aging’s detrimental effects even though there is no one
agreed way for the application of CR. In this study, varying levels of CRs were
applied for differing durations to MMTV-TGF-alpha female mice. The study
initiated when mice were 10-weeks of age (Baseline) and carried out until 49/50
weeks of age and 81/82 weeks of age. There were four dietary groups named Adlibitum (AL; control), Chronic Calorie Restriction (CCR), Intermittent Calorie Restriction - Restriction (ICR-R), and Intermittent Calorie Restriction -Refeed
(ICR-RF). The study’s first aim was to show age-related changes in the cellular and synaptic proteins and the inflammatory state of the female mice’s brains. The second aim of the study is to demonstrate the effects of varying levels of CR implemented
for the short-term and the long-term manner on the same hallmarks. Our findings showed both chronic- or intermittent- CR altered the synaptic integrity proteins against brain aging at the long-term period (81/82 weeks) compared to the
short-term (49/50 weeks) period except for PSD-95. Similarly, both chronic- or
intermittent- CR showed an attenuative impact on the pro-inflammatory markers, but IL-6 was affected only by CCR at the same periods. Furthermore, an age-related imbalance between neurogenesis and astrogliogenesis was shown based
on DCX and GFAP. Both chronic- or intermittent- CR showed a compensatory
effect on it acting through astrogliogenesis, even though it was not statistically
significant.
Keywords
Brain agingCalorie restriction
Proliferation
Synaptic integrity
Neuroinflammation
Western blot
Female mouse