Document Type and Release Option
Thesis (open access)
Dr. Rebecca Kocerha
MicroRNAs are noncoding RNAs found in cells and the bloodstream, which help to maintain proper protein production and overall gene expression1. Typically, microRNAs bind to messenger RNA (mRNA) in the cell cytoplasm, acting as post-transcriptional regulators, and either degrade or repress mRNA2. Due to microRNAs playing a vital role in gene expression by repressing protein production of target genes, if they are underexpressed then the protein it regulates could be overexpressed as a result.
miRNAs have the potential to be biomarkers for numerous neurodegenerative diseases. Neurodegeneration can be seen in many forms such as Dementia, Alzheimer’s (AD), Huntington’s Disease (HD), Creutzfeldt-Jakob Disease (CJD), Vascular Dementia (VD), Dementia With Lewy Bodies (DLB), and Parkinson's Disease Dementia (PD). Early diagnosis of neurodegenerative disease is difficult due to the inability to analyze the diseased tissue. Tissue in the central nervous system cannot be biopsied without using invasive techniques. miRNAs originating from not easily accessible locations, such as neurons in the brain and spinal cord, have the ability to detect early biomarkers for dementia. With the analysis of miRNAs as biomarkers for dementia, early diagnosis of neurodegeneration may be facilitated.
Sleep deprivation (SD) is one of the many side effects, and causes, of neurodegeneration and it adversely affects the circadian physiology3. To investigate abnormal microRNA expression, Danio rerio (zebrafish) will be used as a model organism and will be exposed to altered circadian rhythms in order to mimic SD. Collection of brain tissue from zebrafish will be conducted to assess for dysregulation of miRNAs.
By altering the circadian rhythm of zebrafish and causing a disruption in the SCN portion of the brain, SD can be mimicked. Neurodegeneration in the form of Dementia, AD, HD, CJD, VD, DLB, and PD can cause many forms of ailments, including SD. Using the zebrafish with altered circadian rhythms, a miRNA analysis could be done on dissected brain sections to analyze the dysregulation of specific miRNAs of interest. The information collected from Target Scan indicates that the following miRNAs may be of particular interest and could be targeted in a miRNA analysis: miRNA family miR-149-5p, miR-5692a, miR-4729, miR-5692a, miR-548e-5p, miR524-5p, miR-520d-5p, and miRNA let-7i-5p. By running an experimental analysis on the dissected brain tissue and targeting specific miRNAs, a set of miRNAs could be found that are consistently dysregulated. These miRNAs could then be further tested using human samples and then targeted in those who have a predisposition for neurodegeneration. Identifying miRNAs that are dysregulated in those with neurodegeneration could help in early diagnosis of the disease.
Coursey, Layton F., "Bioinformatic analysis of miRNA mechanisms in circadian rhythm using a zebrafish (Danio Rerio) model" (2023). Honors College Theses. 872.