Increased circulating microRNAs miR-342-3p and miR-21-5p in natural sheep prion disease

Abstract

Scrapie is a transmissible spongiform encephalopathy (TSE), or prion disease, of sheep and goats. As no simple diagnostic tests are yet available to detect TSEs in vivo, easily accessible biomarkers could facilitate the eradication of scrapie agents from the food chain. To this end, we analysed by quantitative reverse transcription PCR a selected set of candidate microRNAs (miRNAs) from circulating blood plasma of naturally infected, classical scrapie sheep that demonstrated clear scrapie symptoms and pathology. Significant scrapie-associated increase was repeatedly found for miR-342-3p and miR-21-5p. This is the first demonstration, to our knowledge, of circulating miRNA alterations in any animal suffering from TSE. Genome-wide expression studies are warranted to investigate the true depth of miRNA alterations in naturally occurring TSEs, especially in presymptomatic animals, as the presented study demonstrates the potential feasibility of miRNAs as circulating TSE biomarkers.

MicroRNA Alterations in the Brain and Body Fluids of Humans and Animal Prion Disease Models: Current Status and Perspectives

“…Regarding the diagnostic potential of miRNAs in prion diseases utilizing less invasive sampling methods, a recent study reported increased levels of circulating miR-342-3p and miR-21-5p in the plasma of sheep naturally affected by scrapie ( Rubio et al, 2017 ), encouraging high-throughput analyses of plasma miRNAs in animal and human prion disease cases in relation to control samples and further validation of the most potent targets.…”

MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease

“…The relatively straightforward detection methods combined with the exceptional stability of miRNAs in the biofluids, such as blood plasma, cerebrospinal fluid (CSF), urine, or saliva, would ideally permit easily obtained diagnostic and/or prognostic tools for NDD. In the context of prion diseases such circulating biomarker candidates have been previously characterized in two targeted candidate studies: one in plasma of sheep naturally infected with scrapie [ 5 ] and another in CSF of sCJD patients [ 4 ]. Curiously, in both studies, the alterations observed in the biofluids were not observed in the central nervous system (CNS), suggesting the possibility that the tissue source(s) of altered miRNAs in biofluids are not necessarily those primarily involved in the pathogenesis.…”

Genome‐wide identification of microRNAs regulating the human prion protein

“…No other screening hit except for miR‐124‐3p has been documented as being consistently altered during prion disease. miR‐146a‐5p and miR‐342‐3p, which have been found to be deregulated in multiple TSEs , had no effect on PrP C expression levels.…”

“…Several miRNAs, most notably miR‐124‐3p, miR‐146a‐5p and miR‐342‐3p, have been found to become consistently deregulated following prion infection in GT1‐7 neuronal cells , RML inoculation in mice , scrapie infection in sheep , BSE infection in macaques and sporadic Creutzfeldt‐Jakob disease (sCJD) in humans . These miRNAs also display similar spatiotemporal expression patterns during prion disease pathogenesis and in sCJD subtypes , implying that mechanisms of deregulation may be conserved across species.…”