THESIS
2021
1 online resource (ix, 54 pages) : color illustrations
Abstract
Mild traumatic brain injury (mTBI), also known as concussions, is a vastly common neurologic
disorder that afflicts people of all ages and background. Although most people who suffer from mTBI
recover after the initial trauma, there is mounting evidence that mTBI is a potential risk factor for
neurodegenerative diseases development. Numerous studies have characterized the pathophysiology of mTBI
at different time points post injury and have found ionic imbalances, diffuse axonal injury and myelin
abnormalities in animal models of mTBI. However, alterations in the epigenome and the transcriptome
associated with mTBI has not been clearly defined. Additionally, the role of the non-coding genome,
including cis-regulatory elements and retrotransposons, has not been explored in mTBI. Thus, th...[
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Mild traumatic brain injury (mTBI), also known as concussions, is a vastly common neurologic
disorder that afflicts people of all ages and background. Although most people who suffer from mTBI
recover after the initial trauma, there is mounting evidence that mTBI is a potential risk factor for
neurodegenerative diseases development. Numerous studies have characterized the pathophysiology of mTBI
at different time points post injury and have found ionic imbalances, diffuse axonal injury and myelin
abnormalities in animal models of mTBI. However, alterations in the epigenome and the transcriptome
associated with mTBI has not been clearly defined. Additionally, the role of the non-coding genome,
including cis-regulatory elements and retrotransposons, has not been explored in mTBI. Thus, there are two
main objectives of this present study. First, I aim to profile the epigenomic and transcriptomic response to
single injury (1xmTBI) and double injuries (2xmTBI) in a rat model of mTBI. Second, I investigated whether
retrotransposons are dysregulated upon 1xmTBI and 2xmTBI. To achieve the aforementioned objectives,
RNA-seq, H3K27ac μChIP-seq, and ATAC-seq datasets were generated from the middle cortex of control
(sham), 1xmTBI, and 2xmTBI rats. Preliminary results show that immune response genes are upregulated in
1xmTBI, while neuroprotective genes are upregulated in 2xmTBI animals. Epigenomic data also reveals the
similarity in chromatin states between sham and 2xmTBI, while 1xmTBI has its own unique epigenomic
signatures. Furthermore, retrotransposons are dysregulated in injury rats compared to sham. Altogether, this
present work provides a first glimpse into how mTBI alters the regulatory epigenetic landscape,
transcriptional response, and retrotransposon activity in the brain.
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