Neurodegeneration in the mice brain: Effects of calorie restriction on sirtuin protein levels

Neurodegenerative (ND) disorders affect a significant portion of the world's population. Alzheimer's disease and Parkinson's disease are gaining importance as a significant public health problem. Despite many advancements in current medicine and clarification of the molecular pathways involved in neurodegeneration, these diseases are progressive and there is no cure at the moment. Calorie restriction (CR) is accomplished as a neuroprotective method and have beneficial roles in the metabolism. CR is suggested to activate protective mechanisms in ND and age-related diseases. There are different types of established CR models. It is shown that CR extended the life-span by increasing the activity of the Sirtuins (SIRT). SIRT are a family of proteins which are histone deacetylases bound to nicotinamide adenine dinucleotide. They were identified as genetic silencing factors and were found to prolong life in the yeast. When the histones are deacetylated by SIRT, the chromatin is closed, or tightly and precisely wound, meaning gene expression is stopped, or silenced, protecting the DNA from damage. SIRT have a protective role in ND diseases related to aging. SIRT 1, 3, and 6 have critical roles in the brain. In this research study we have tested the effect of different types of CR as chronic CR, or intermittent CR on SIRT levels and neurodegeneration in the mice brain. SIRT 1, SIRT 3 and SIRT 6 protein levels were measured via ELISA method. Neurodegeneration was evaluated by fluoro-jade fluorescein staining and image-based quantification method. We found significantly increased mean SIRT values in CR groups compared to Ad-libitum and baseline controls. Fluoro-jade image quantification results revealed significantly increased neurodegeneration in ad-libitum compared to CR groups. We have concluded that different types of CR prevents neurodegeneration in the mice and SIRT are involved in this process. Our findings of significantly increased SIRT expression and decreased neurodegeneration after intermittent CR is a novel contribution which can be a therapeutic strategy in the treatment of ND diseases in the future. Key Words: Ad libitum, calorie restriction, ELISA, fluoro jade, mice brain, neurodegeneration, sirtuin