Improved detection of RNA foci in amyotrophic lateral sclerosis post-mortem tissue using BaseScope™ shows a lack of association with cognitive dysfunction.
|Title||Improved detection of RNA foci in amyotrophic lateral sclerosis post-mortem tissue using BaseScope™ shows a lack of association with cognitive dysfunction.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Mehta AR, Selvaraj BT, Barton SK, McDade K, Abrahams S, Chandran S, Smith C, Gregory JM|
|Date Published||2020 Jan 31|
The 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, RNA foci have been identified using hybridization. Here, we have implemented BaseScope™, a high-resolution modified 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 antisense RNA foci in post-mortem brain and spinal cord tissue of six deeply clinically phenotyped 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 ( = 0.93; = 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 antisense RNA foci in .
|Alternate Journal||Brain Commun|
|PubMed Central ID||PMC7099934|
|Grant List||MR/R001162/1 / MRC_ / Medical Research Council / United Kingdom|