Improved detection of RNA foci in C9orf72 amyotrophic lateral sclerosis post-mortem tissue using BaseScope™ shows a lack of association with cognitive dysfunction
| العنوان: | Improved detection of RNA foci in C9orf72 amyotrophic lateral sclerosis post-mortem tissue using BaseScope™ shows a lack of association with cognitive dysfunction |
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| المؤلفون: | Jenna M. Gregory, Karina McDade, Siddharthan Chandran, Arpan R Mehta, Samantha K. Barton, Bhuvaneish T. Selvaraj, Colin Smith, Sharon Abrahams |
| المصدر: | Brain communications Mehta, A R, Selvaraj, B T, Barton, S K, Mcdade, K, Abrahams, S, Chandran, S, Smith, C & Gregory, J M 2020, ' Improved detection of RNA foci in C9orf72 amyotrophic lateral sclerosis post-mortem tissue using BaseScope™ shows a lack of association with cognitive dysfunction ', Brain Communications, vol. 2, no. 1, fcaa009 . https://doi.org/10.1093/braincomms/fcaa009 |
| بيانات النشر: | Oxford University Press (OUP), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | cognition, 0301 basic medicine, Pathology, medicine.medical_specialty, Cell type, TDP-43, sense RNA foci, In situ hybridization, Biology, Article, 03 medical and health sciences, 0302 clinical medicine, C9orf72, Sense (molecular biology), medicine, Amyotrophic lateral sclerosis, antisense RNA foci, General Engineering, RNA, Spinal cord, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, ALS, Trinucleotide repeat expansion, 030217 neurology & neurosurgery |
| الوصف: | The C9orf72 hexanucleotide repeat expansion is the commonest known genetic mutation in amyotrophic lateral sclerosis. A neuropathological hallmark is the intracellular accumulation of RNA foci. The role that RNA foci play in the pathogenesis of amyotrophic lateral sclerosis is widely debated. Historically, C9orf72 RNA foci have been identified using in situ hybridization. Here, we have implemented BaseScope™, a high-resolution modified in situ hybridization technique. We demonstrate that previous studies have underestimated the abundance of RNA foci in neurons and glia. This improved detection allowed us to investigate the abundance, regional distribution and cell type specificity of sense C9orf72 RNA foci in post-mortem brain and spinal cord tissue of six deeply clinically phenotyped C9orf72 patients and six age- and sex-matched controls. We find a correlation between RNA foci and the accumulation of transactive response DNA-binding protein of 43 kDa in spinal motor neurons (rs = 0.93; P = 0.008), but not in glia or cortical motor neurons. We also demonstrate that there is no correlation between the presence of RNA foci and the accumulation of transactive response DNA binding protein of 43 kDa in extra-motor brain regions. Furthermore, there is no association between the presence of RNA foci and cognitive indices. These results highlight the utility of BaseScope™ in the clinicopathological assessment of the role of sense RNA foci in C9orf72. |
| وصف الملف: | application/pdf |
| تدمد: | 2632-1297 |
| DOI: | 10.1093/braincomms/fcaa009 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6ed885757c8f80d35254e180cb7a9bbc https://doi.org/10.1093/braincomms/fcaa009 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6ed885757c8f80d35254e180cb7a9bbc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 26321297 |
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| DOI: | 10.1093/braincomms/fcaa009 |