title: MicroRNA abundance is altered in synaptoneurosomes during prion disease.
abstract: Discrepancy in synaptic structural plasticity is one of the earliest manifestations of the neurodegenerative state. In prion diseases, a reduction in synapses and dendritic spine densities is observed during preclinical disease in neurons of the cortex and hippocampus. The underlying molecular mechanisms of these alterations have not been identified but microRNAs (miRNAs), many of which are enriched at the synapse, likely regulate local protein synthesis in rapid response to stressors such as replicating prions. MiRNAs are therefore candidate regulators of these early neurodegenerative changes and may provide clues as to the molecular pathways involved. We therefore determined changes in mature miRNA abundance within synaptoneurosomes isolated from prion-infected, as compared to mock-infected animals, at asymptomatic and symptomatic stages of disease. During preclinical disease, miRNAs that are enriched in neurons including miR-124a-3p, miR-136-5p and miR-376a-3p were elevated. At later stages of disease we found increases in miRNAs that have previously been identified as deregulated in brain tissues of prion infected mice, as well as in Alzheimer's disease (AD) models. These include miR-146a-5p, miR-142-3p, miR-143-3p, miR-145a-5p, miR-451a, miR-let-7b, miR-320 and miR-150-5p. A number of miRNAs also decreased in abundance during clinical disease. These included almost all members of the related miR-200 family (miR-200a-3p, miR-200b-3p, miR-200c-3p, miR-141-3p, and miR-429-3p) and the 182 cluster (miR-182-5p and miR-183-5p).
authors.affiliation: Molecular PathoBiology, Public Health Agency of Canada, National Microbiology Laboratory, 1015 Arlington St., Winnipeg, MB R3E 3R2, Canada; Department of Medical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of Manitoba, 730 William Ave., Winnipeg, MB R3E 0W3, Canada.
authors.forename: Amrit S
authors.initials: AS
authors.lastname: Boese
authors.affiliation: Molecular PathoBiology, Public Health Agency of Canada, National Microbiology Laboratory, 1015 Arlington St., Winnipeg, MB R3E 3R2, Canada.
authors.forename: Reuben
authors.initials: R
authors.lastname: Saba
authors.affiliation: Molecular PathoBiology, Public Health Agency of Canada, National Microbiology Laboratory, 1015 Arlington St., Winnipeg, MB R3E 3R2, Canada; Department of Medical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of Manitoba, 730 William Ave., Winnipeg, MB R3E 0W3, Canada.
authors.forename: Kristyn
authors.initials: K
authors.lastname: Campbell
authors.affiliation: Molecular PathoBiology, Public Health Agency of Canada, National Microbiology Laboratory, 1015 Arlington St., Winnipeg, MB R3E 3R2, Canada; Department of Medical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of Manitoba, 730 William Ave., Winnipeg, MB R3E 0W3, Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Majer
authors.affiliation: Molecular PathoBiology, Public Health Agency of Canada, National Microbiology Laboratory, 1015 Arlington St., Winnipeg, MB R3E 3R2, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Medina
authors.affiliation: National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, 1015 Arlington St., Winnipeg, MB R3E 3M4, Canada.
authors.forename: Lynn
authors.initials: L
authors.lastname: Burton
authors.affiliation: Viral Diseases Division, Public Health Agency of Canada, National Microbiology Laboratory, 1015 Arlington St., Winnipeg, MB R3E 3R2, Canada.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Booth
authors.affiliation: Mass Spectrometry and Proteomics Core Facility, Public Health Agency of Canada, National Microbiology Laboratory, 1015 Arlington St., Winnipeg, MB R3E 3R2, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Chong
authors.affiliation: Mass Spectrometry and Proteomics Core Facility, Public Health Agency of Canada, National Microbiology Laboratory, 1015 Arlington St., Winnipeg, MB R3E 3R2, Canada.
authors.forename: Garrett
authors.initials: G
authors.lastname: Westmacott
authors.affiliation: Thermo Fisher Scientific, San Jose, CA, USA.
authors.forename: Sucharita M
authors.initials: SM
authors.lastname: Dutta
authors.affiliation: Thermo Fisher Scientific, San Jose, CA, USA.
authors.forename: Julian A
authors.initials: JA
authors.lastname: Saba
authors.affiliation: Molecular PathoBiology, Public Health Agency of Canada, National Microbiology Laboratory, 1015 Arlington St., Winnipeg, MB R3E 3R2, Canada; Department of Medical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of Manitoba, 730 William Ave., Winnipeg, MB R3E 0W3, Canada. Electronic address: Stephanie.Booth@phac-aspc.gc.ca.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Booth
mesh_terms: D000818:Animals; D003712:Dendrites / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D017096:Prion Diseases / Q000378:metabolism*; D011328:Prions / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D011328:Prions
keywords: Dendrite; MiRNA; Neurodegeneration; Prion disease; Synapse; Synaptoneurosome