Plasma microRNA miR-26b as a potential diagnostic biomarker of degenerative myelopathy in Pembroke welsh corgis

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Degenerative myelopathy (DM) is a progressive neurodegenerative disease frequently found in Pembroke Welsh Corgis (PWCs). Most DM-affected PWCs are homozygous for the mutant superoxide dismutase 1 ( SOD1) allele; however, the genetic examination for the SOD1 mutation does not exclusively detect symptomatic dogs. In order to identify novel biomarkers, the plasma microRNA (miRNA) profiles of PWCs with DM were investigated.

Results

Quantification of the plasma levels of 277 miRNAs by an RT-qPCR array identified 11 up-regulated miRNAs and 7 down-regulated miRNAs in DM-affected PWCs from those in wild-type SOD1 PWCs. A pathway analysis identified 3 miRNAs: miR-26b, miR-181a, and miR-196a, which potentially regulate several genes associated with SOD1. In order to validate the diagnostic accuracy of the candidate miRNAs in the aged PWC population, candidate miRNAs in plasma were measured by RT-qPCR and a receiver operating characteristic (ROC) curve analysis was performed. miR-26b had the largest area under the ROC curve for distinguishing DM PWCs from healthy PWCs (sensitivity, 66.7%; specificity, 87.0%). The plasma level of miR-26b was significantly higher in the DM group than in the healthy control group. A positive correlation was observed between increases in the plasma level of miR-26b and disease progression.

Conclusions

These results suggest that plasma miR-26b is a potential novel diagnostic biomarker of DM.

Electronic supplementary material

The online version of this article (10.1186/s12917-019-1944-3) contains supplementary material, which is available to authorized users.

Related collections

Most cited references 30

Record: found
Abstract: found
Article: not found

Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory.

Paul R. Turner, Kate O’Connor, Warren Tate … (2003)

Amyloid-beta precursor protein (APP) is a membrane-spanning protein with a large extracellular domain and a much smaller intracellular domain. It is the source of the amyloid-beta (Abeta) peptide found in neuritic plaques of Alzheimer's disease (AD) patients. Because Abeta shows neurotoxic properties, and because familial forms of AD promote Abeta accumulation, a massive international research effort has been aimed at understanding the mechanisms of Abeta generation, catabolism and toxicity. APP, however, is an extremely complex molecule that may be a functionally important molecule in its full-length configuration, as well as being the source of numerous fragments with varying effects on neural function. For example, one fragment derived from the non-amyloidogenic processing pathway, secreted APPalpha (sAPPalpha), is neuroprotective, neurotrophic and regulates cell excitability and synaptic plasticity, while Abeta appears to exert opposing effects. Less is known about the neural functions of other fragments, but there is a growing interest in understanding the basic biology of APP as it has become recognized that alterations in the functional activity of the APP fragments during disease states will have complex effects on cell function. Indeed, it has been proposed that reductions in the level or activity of certain APP fragments, in addition to accumulation of Abeta, may play a critical role in the cognitive dysfunction associated with AD, particularly early in the course of the disease. To test and modify this hypothesis, it is important to understand the roles that full-length APP and its fragments normally play in neuronal structure and function. Here we review evidence addressing these fundamental questions, paying particular attention to the contributions that APP fragments play in synaptic transmission and neural plasticity, as these may be key to understanding their effects on learning and memory. It is clear from this literature that APP fragments, including Abeta, can exert a powerful regulation of key neural functions including cell excitability, synaptic transmission and long-term potentiation, both acutely and over the long-term. Furthermore, there is a small but growing literature confirming that these fragments correspondingly regulate behavioral learning and memory. These data indicate that a full account of cognitive dysfunction in AD will need to incorporate the actions of the full complement of APP fragments. To this end, there is an urgent need for a dedicated research effort aimed at understanding the behavioral consequences of altered levels and activity of the different APP fragments as a result of experience and disease.

0 comments Cited 163 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis.

Tomoyuki Awano, Gary S. Johnson, Claire Wade … (2009)

Canine degenerative myelopathy (DM) is a fatal neurodegenerative disease prevalent in several dog breeds. Typically, the initial progressive upper motor neuron spastic and general proprioceptive ataxia in the pelvic limbs occurs at 8 years of age or older. If euthanasia is delayed, the clinical signs will ascend, causing flaccid tetraparesis and other lower motor neuron signs. DNA samples from 38 DM-affected Pembroke Welsh corgi cases and 17 related clinically normal controls were used for genome-wide association mapping, which produced the strongest associations with markers on CFA31 in a region containing the canine SOD1 gene. SOD1 was considered a regional candidate gene because mutations in human SOD1 can cause amyotrophic lateral sclerosis (ALS), an adult-onset fatal paralytic neurodegenerative disease with both upper and lower motor neuron involvement. The resequencing of SOD1 in normal and affected dogs revealed a G to A transition, resulting in an E40K missense mutation. Homozygosity for the A allele was associated with DM in 5 dog breeds: Pembroke Welsh corgi, Boxer, Rhodesian ridgeback, German Shepherd dog, and Chesapeake Bay retriever. Microscopic examination of spinal cords from affected dogs revealed myelin and axon loss affecting the lateral white matter and neuronal cytoplasmic inclusions that bind anti-superoxide dismutase 1 antibodies. These inclusions are similar to those seen in spinal cord sections from ALS patients with SOD1 mutations. Our findings identify canine DM to be the first recognized spontaneously occurring animal model for ALS.

0 comments Cited 79 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Circulating cell-free microRNA as biomarkers for screening, diagnosis and monitoring of neurodegenerative diseases and other neurologic pathologies

Kira S. Sheinerman, Samuil Umansky (2013)

Many neurodegenerative diseases, such as Alzheimer's disease, Parkinson disease, vascular and frontotemporal dementias, as well as other chronic neurological pathologies, are characterized by slow development with a long asymptomatic period followed by a stage with mild clinical symptoms. As a consequence, these serious pathologies are diagnosed late in the course of a disease, when massive death of neurons has already occurred and effective therapeutic intervention is problematic. Thus, the development of screening tests capable of detecting neurodegenerative diseases during early, preferably asymptomatic, stages is a high unmet need. Since such tests are to be used for screening of large populations, they should be non-invasive and relatively inexpensive. Further, while subjects identified by screening tests can be further tested with more invasive and expensive methods, e.g., analysis of cerebrospinal fluid or imaging techniques, to be of practical utility screening tests should have high sensitivity and specificity. In this review, we discuss advantages and disadvantages of various approaches to developing screening tests based on analysis of circulating cell-free microRNA (miRNA). Applications of circulating miRNA-based tests for diagnosis of acute and chronic brain pathologies, for research of normal brain aging, and for disease and treatment monitoring are also discussed.

0 comments Cited 78 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Kohei Nakata: k.nakata.1986@gmail.com

Kazuki Heishima: kheishima@live.jp

Hiroki Sakai: shiroki@gifu-u.ac.jp

Osamu Yamato: osam@vet.kagoshima-u.ac.jp

Yu Furusawa: yu_furusawa728@yahoo.co.jp

Hidetaka Nishida: hnishida@vet.osakafu-u.ac.jp

Sadatoshi Maeda: sadat@gifu-u.ac.jp

Hiroaki Kamishina:

ORCID: http://orcid.org/0000-0001-9929-6654

kamicna@gifu-u.ac.jp

Journal

Journal ID (nlm-ta): BMC Vet Res

Journal ID (iso-abbrev): BMC Vet. Res

Title: BMC Veterinary Research

Publisher: BioMed Central (London )

ISSN (Electronic): 1746-6148

Publication date (Electronic): 10 June 2019

Publication date PMC-release: 10 June 2019

Publication date Collection: 2019

Volume: 15

Electronic Location Identifier: 192

Affiliations

[1 ]ISNI 0000 0004 0370 4927, GRID grid.256342.4, The United Graduate School of Veterinary Sciences, , Gifu University, ; 1-1 Yanagido, Gifu, 501-1193 Japan

[2 ]ISNI 0000 0004 0370 4927, GRID grid.256342.4, The United Graduate School of Veterinary Sciences and Center for Highly Advanced Integration of Nano and Life Sciences, , Gifu University, ; 1-1 Yanagido, Gifu, 501-1193 Japan

[3 ]ISNI 0000 0001 1167 1801, GRID grid.258333.c, Joint Faculty of Veterinary Medicine, , Kagoshima University, ; 1-21-24 Kohrimoto, Kagoshima, 890-0065 Japan

Author information

Hiroaki Kamishina http://orcid.org/0000-0001-9929-6654

Article

Publisher ID: 1944

DOI: 10.1186/s12917-019-1944-3

PMC ID: 6558770

PubMed ID: 31182094

SO-VID: 711eb384-6041-4fc0-af42-2034020366f8

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 9 June 2018

Date accepted : 4 June 2019

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100012834, Gifu University;

Custom metadata

ScienceOpen disciplines: Veterinary medicine

Keywords: canine,degenerative myelopathy,microrna,diagnostic biomarker,neurology

Data availability:

ScienceOpen disciplines: Veterinary medicine

Keywords: canine, degenerative myelopathy, microrna, diagnostic biomarker, neurology

Plasma microRNA miR-26b as a potential diagnostic biomarker of degenerative myelopathy in Pembroke welsh corgis

Read this article at

Abstract

Background

Results

Conclusions

Electronic supplementary material

Related collections

Horses and Humans Research Foundation

Most cited references 30

Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory.

Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis.

Circulating cell-free microRNA as biomarkers for screening, diagnosis and monitoring of neurodegenerative diseases and other neurologic pathologies

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 117

Cited by 5

Most referenced authors 866