Investigating epigenomic and transcriptomic changes induced by mild traumatic brain injuries

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, 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.

Date of Award	2021
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Danny Chi Yeu LEUNG (Supervisor)