title: MicroRNA and mRNA Transcriptome Profiling in Primary Human Astrocytes Infected with Borrelia burgdorferi.
abstract: Lyme disease is caused by infection with the bacterium Borrelia burgdorferi (Bb), which is transmitted to humans by deer ticks. The infection manifests usually as a rash and minor systemic symptoms; however, the bacteria can spread to other tissues, causing joint pain, carditis, and neurological symptoms. Lyme neuroborreliosis presents itself in several ways, such as Bell's palsy, meningitis, and encephalitis. The molecular basis for neuroborreliosis is poorly understood. Analysis of the changes in the expression levels of messenger RNAs and non-coding RNAs, including microRNAs, following Bb infection could therefore provide vital information on the pathogenesis and clinical symptoms of neuroborreliosis. To this end, we used cultured primary human astrocytes, key responders to CNS infection and important components of the blood-brain barrier, as a model system to study RNA and microRNA changes in the CNS caused by Bb. Using whole transcriptome RNA-seq, we found significant changes in 38 microRNAs and 275 mRNAs at 24 and 48 hours following Bb infection. Several of the RNA changes affect pathways involved in immune response, development, chromatin assembly (including histones) and cell adhesion. Further, several of the microRNA predicted target mRNAs were also differentially regulated. Overall, our results indicate that exposure to Bb causes significant changes to the transcriptome and microRNA profile of astrocytes, which has implications in the pathogenesis, and hence potential treatment strategies to combat this disease.
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States of America.
authors.forename: Timothy
authors.initials: T
authors.lastname: Casselli
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States of America.
authors.forename: Humaira
authors.initials: H
authors.lastname: Qureshi
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Peterson
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States of America.
authors.forename: Danielle
authors.initials: D
authors.lastname: Perley
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States of America.
authors.forename: Emily
authors.initials: E
authors.lastname: Blake
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States of America.
authors.forename: Bradley
authors.initials: B
authors.lastname: Jokinen
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States of America.
authors.forename: Ata
authors.initials: A
authors.lastname: Abbas
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States of America.
authors.forename: Sergei
authors.initials: S
authors.lastname: Nechaev
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States of America.
authors.forename: John A
authors.initials: JA
authors.lastname: Watt
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States of America.
authors.forename: Archana
authors.initials: A
authors.lastname: Dhasarathy
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States of America.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Brissette
mesh_terms: D001253:Astrocytes / Q000378:metabolism* / Q000382:microbiology*; D025065:Borrelia burgdorferi / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007109:Immunity / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D008193:Lyme Disease / Q000235:genetics* / Q000382:microbiology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D022661:RNA, Untranslated; D014157:Transcription Factors