Master of Science (M.S.)
Degree Granting Department
Biology (Cell Biology, Microbiology, Molecular Biology)
Stanley M. Stevens, Ph.D.
Brant R. Burkhardt, Ph.D.
Bin Xue, Ph.D.
Bin Liu, Ph.D.
Caralina Marín De Evsikova, Ph.D.
alcohol, ethanol, microglia, microRNA, proteome, transcriptome
Chronic consumption of, and acute intoxication from, alcohol can have profound effects on the functional integrity of the central nervous system (CNS). The resident immunomodulatory cells of the CNS, microglia, provide signaling factors with both pro- and anti-inflammatory effects for protection. Microglial activation ranges through a multiplex of phases, of which have yet to be defined when induced by exposure to alcohol, and how the activation impacts surrounding cells. Exposure of alcohol has been revealed to induce an immune response in microglia, which can exhibit characteristics unique to a pro-inflammatory response depending on dose and time of alcohol exposure. To define the activation state produced by microglia in response to alcohol, ethanol-induced microglial protein and microRNA (miRNA) global profile expression changes were obtained in vitro, using the BV2 murine microglial cells, using mass spectrometry (MS)-based proteomics and microarray-based transcriptomic approaches, respectively, revealing potential regulatory miRNAs for inflammation mediation. The 2,277 protein groups identified through mass spectrometry and 3,195 miRNA genes identified using microarray analysis provided a strong foundation to determine miRNA-mRNA regulators and the pathways in which they are involved, that potentially play a role in microglial activation. The comparison of the miRNA expressed in microglia after lipopolysaccharide (LPS) and ethanol (EtOH) exposure, indicate that EtOH influenced miRNA does not signify having a pro-inflammatory activation phenotype, but the miRNA expressed under the influence of LPS does support this phenotype. The global pathway regulation evidence and defined proteins and miRNA-mRNA interactions upon microglial activation have the possibility to unite the pathways described in previous studies and further our understanding of EtOH-induced microglial activation, and their role in neuroinflammation and neurodegeneration. Further research to determine and validate the extent of gene regulation by miRNAs and subsequent impact on specific protein levels should be employed to define the miRNA transcriptome influence on pathways relevant to microglial function.
Scholar Commons Citation
Cook, Brandi Jo, "Identification of Regulatory miRNAs Associated with Ethanol-Induced Microglial Activation Using Integrated Proteomic and Transcriptomic Approaches" (2018). Graduate Theses and Dissertations.