Neurogranin and Neurofilament Light Chain as Preclinical Biomarkers in Scrapie
Prion diseases are diagnosed in the symptomatic stage, when the neuronal damage is spread throughout the central nervous system (CNS). The assessment of biological features that allow the detection of asymptomatic cases is needed, and, in this context, scrapie, where pre-symptomatic infected animals...
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/13/7182 |
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| author | Marina Betancor Sonia Pérez-Lázaro Alicia Otero Belén Marín Inmaculada Martín-Burriel Kaj Blennow Juan José Badiola Henrik Zetterberg Rosa Bolea |
| author_facet | Marina Betancor Sonia Pérez-Lázaro Alicia Otero Belén Marín Inmaculada Martín-Burriel Kaj Blennow Juan José Badiola Henrik Zetterberg Rosa Bolea |
| author_sort | Marina Betancor |
| collection | DOAJ |
| description | Prion diseases are diagnosed in the symptomatic stage, when the neuronal damage is spread throughout the central nervous system (CNS). The assessment of biological features that allow the detection of asymptomatic cases is needed, and, in this context, scrapie, where pre-symptomatic infected animals can be detected through rectal biopsy, becomes a good study model. Neurogranin (Ng) and neurofilament light chain (NfL) are proteins that reflect synaptic and axonal damage and have been studied as cerebrospinal fluid (CSF) biomarkers in different neurodegenerative disorders. In this study, we evaluated Ng and NfL both at the protein and transcript levels in the CNS of preclinical and clinical scrapie-affected sheep compared with healthy controls and assessed their levels in ovine CSF. The correlation between these proteins and the main neuropathological events in prion diseases, PrP<sup>Sc</sup> deposition and spongiosis, was also assessed. The results show a decrease in Ng and NfL at the protein and gene expression levels as the disease progresses, and significant changes between the control and preclinical animals. On the contrary, the CSF levels of NfL increased throughout the progression of the disease. Negative correlations between neuropathological markers of prion disease and the concentration of the studied proteins were also found. Although further research is needed, these results suggest that Ng and NfL could act as biomarkers for neurodegeneration onset and intensity in preclinical cases of scrapie. |
| first_indexed | 2024-03-09T21:50:02Z |
| format | Article |
| id | doaj.art-96a66dbcde7840b0ad2329f4091fa4e9 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:50:02Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-96a66dbcde7840b0ad2329f4091fa4e92023-11-23T20:09:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012313718210.3390/ijms23137182Neurogranin and Neurofilament Light Chain as Preclinical Biomarkers in ScrapieMarina Betancor0Sonia Pérez-Lázaro1Alicia Otero2Belén Marín3Inmaculada Martín-Burriel4Kaj Blennow5Juan José Badiola6Henrik Zetterberg7Rosa Bolea8Centro de Encefalopatías y Enfermedades Transmisibles Emergentes, Universidad de Zaragoza, IA2, IIS Aragon, 50009 Zaragoza, SpainCentro de Encefalopatías y Enfermedades Transmisibles Emergentes, Universidad de Zaragoza, IA2, IIS Aragon, 50009 Zaragoza, SpainCentro de Encefalopatías y Enfermedades Transmisibles Emergentes, Universidad de Zaragoza, IA2, IIS Aragon, 50009 Zaragoza, SpainCentro de Encefalopatías y Enfermedades Transmisibles Emergentes, Universidad de Zaragoza, IA2, IIS Aragon, 50009 Zaragoza, SpainCentro de Encefalopatías y Enfermedades Transmisibles Emergentes, Universidad de Zaragoza, IA2, IIS Aragon, 50009 Zaragoza, SpainDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy, University of Gothenburg, 405 30 Mölndal, SwedenCentro de Encefalopatías y Enfermedades Transmisibles Emergentes, Universidad de Zaragoza, IA2, IIS Aragon, 50009 Zaragoza, SpainDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy, University of Gothenburg, 405 30 Mölndal, SwedenCentro de Encefalopatías y Enfermedades Transmisibles Emergentes, Universidad de Zaragoza, IA2, IIS Aragon, 50009 Zaragoza, SpainPrion diseases are diagnosed in the symptomatic stage, when the neuronal damage is spread throughout the central nervous system (CNS). The assessment of biological features that allow the detection of asymptomatic cases is needed, and, in this context, scrapie, where pre-symptomatic infected animals can be detected through rectal biopsy, becomes a good study model. Neurogranin (Ng) and neurofilament light chain (NfL) are proteins that reflect synaptic and axonal damage and have been studied as cerebrospinal fluid (CSF) biomarkers in different neurodegenerative disorders. In this study, we evaluated Ng and NfL both at the protein and transcript levels in the CNS of preclinical and clinical scrapie-affected sheep compared with healthy controls and assessed their levels in ovine CSF. The correlation between these proteins and the main neuropathological events in prion diseases, PrP<sup>Sc</sup> deposition and spongiosis, was also assessed. The results show a decrease in Ng and NfL at the protein and gene expression levels as the disease progresses, and significant changes between the control and preclinical animals. On the contrary, the CSF levels of NfL increased throughout the progression of the disease. Negative correlations between neuropathological markers of prion disease and the concentration of the studied proteins were also found. Although further research is needed, these results suggest that Ng and NfL could act as biomarkers for neurodegeneration onset and intensity in preclinical cases of scrapie.https://www.mdpi.com/1422-0067/23/13/7182prionprion diseasesscrapiebiomarkersneurodegenerationneurogranin |
| spellingShingle | Marina Betancor Sonia Pérez-Lázaro Alicia Otero Belén Marín Inmaculada Martín-Burriel Kaj Blennow Juan José Badiola Henrik Zetterberg Rosa Bolea Neurogranin and Neurofilament Light Chain as Preclinical Biomarkers in Scrapie International Journal of Molecular Sciences prion prion diseases scrapie biomarkers neurodegeneration neurogranin |
| title | Neurogranin and Neurofilament Light Chain as Preclinical Biomarkers in Scrapie |
| title_full | Neurogranin and Neurofilament Light Chain as Preclinical Biomarkers in Scrapie |
| title_fullStr | Neurogranin and Neurofilament Light Chain as Preclinical Biomarkers in Scrapie |
| title_full_unstemmed | Neurogranin and Neurofilament Light Chain as Preclinical Biomarkers in Scrapie |
| title_short | Neurogranin and Neurofilament Light Chain as Preclinical Biomarkers in Scrapie |
| title_sort | neurogranin and neurofilament light chain as preclinical biomarkers in scrapie |
| topic | prion prion diseases scrapie biomarkers neurodegeneration neurogranin |
| url | https://www.mdpi.com/1422-0067/23/13/7182 |
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