Traumatic brain injury alters expression of hippocampal microRNAs: potential regulators of multiple pathophysiological processes.
Multiple cellular, molecular, and biochemical changes contribute to outcome after traumatic brain injury (TBI). MicroRNAs (miRNAs) are known to influence many important cellular processes, including proliferation, apoptosis, neurogenesis, angiogenesis, and morphogenesis, all processes that are involved in TBI pathophysiology. However, it has not yet been determined whether miRNA expression is altered after TBI. In the present study, we used a microarray platform to examine changes in the hippocampal expression levels of 444 verified rodent miRNAs at 3 and 24 hr after controlled cortical impact injury. Our analysis found 50 miRNAs exhibited decreased expression levels and 35 miRNAs exhibited increased expression levels in the hippocampus after injury. We extended the microarray findings using quantitative polymerase chain reaction analysis for a subset of the miRNAs with altered expression levels (miR-107, -130a, -223, -292-5p, -433-3p, -451, -541, and -711). Bioinformatic analysis of the predicted targets for this panel of miRNAs revealed an overrepresentation of proteins involved in several biological processes and functions known to be initiated after injury, including signal transduction, transcriptional regulation, proliferation, and differentiation. Our results indicate that multiple protein targets and biological processes involved in TBI pathophysiology may be regulated by miRNAs.
Redell
John B
JB
Department of Neurobiology and Anatomy, The University of Texas Medical School, Houston, Texas 77225, USA.
Liu
Yin
Y
Dash
Pramod K
PK
D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D019295:Computational Biology; D015870:Gene Expression; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D025941:Protein Interaction Mapping; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor
D035683:MicroRNAs; D011506:Proteins; D050794:STAT1 Transcription Factor