AUTHOR=Thangavelu Bharani , Wilfred Bernard S. , Johnson David , Gilsdorf Janice S. , Shear Deborah A. , Boutté Angela M. 

TITLE=Penetrating Ballistic-Like Brain Injury Leads to MicroRNA Dysregulation, BACE1 Upregulation, and Amyloid Precursor Protein Loss in Lesioned Rat Brain Tissues

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 14 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2020.00915

DOI=10.3389/fnins.2020.00915

ISSN=1662-453X

ABSTRACT=Severe traumatic brain injury (TBI) is a risk factor for neurodegenerative diseases. Yet, the molecular events involving dysregulated miRNAs that may be associated with protein degradation in the brain remains elusive. Expression patterns of more than 800 miRNA sequences were determined using rat ipsilateral coronal brain tissues collected 1, 3, or 7days (d) after penetrating ballistic-like brain injury (PBBI). As a control for each time-point, Sham animals received craniotomy alone. Microarray and systems biology analysis indicated that the amplitude and complexity of the miRNA gene expression were greatest 7d after PBBI. Arrays and Q-PCR inferred that dysregulation of miR-135a, miR -328, miR-29c, and miR-21 were associated with altered levels of BACE1, PSEN1, PSEN2, and APP genes. These events were followed by increased levels of mature BACE-1 protein and concomitant loss of full length APP within 3-7d, then elevation of Aβ-40 7d after PBBI. This study indicates that miRNA arrays, coupled with systems biology, may be used to guide study design prior validation of miRNA dysregulation. Associative analysis of miRNAs, mRNAs, and proteins within a proposed pathway are poised for further validation as biomarkers and therapeutic targets relevant to TBI-induced APP loss and subsequent Aβ peptide generation during neurodegeneration.