A06 Screening of gene expression and molecular changes in the knock-in minipig model of Huntington's disease. (12th September 2022)

• Record Type: Journal Article
• Authors: Sekac, David; Nemesh, Kateryna; Juhásová, Jana; Juhás, Stefan; Ellederova, Zdenka
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 93(2022)Supplement 1
• Page Start: A2
• Page End: A3
• Publication Date: 2022-09-12
• Subjects: metabolism -- DNA damage -- RNA sequencing -- putamen -- porcine model; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2022-ehdn.6
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Background: Mutated huntingtin affects many cellular processes. Disruption in energy metabolism and DNA damage repair belong to them. However, the primary cause leading to neurodegeneration is not well known. The atrophy starts from the caudate nucleus and putamen, making this tissue's transcriptome a subject of special interest. Aims: We aim to detect earlier molecular changes in the pre-symptomatic age of the HD minipig model, which could help find a biomarker for the HD onset and/or reflect HD progression by invasive and non-invasive methods. Methods/Techniques: We isolate primary skin fibroblasts and polymorphonuclear blood cells (PBMC) from knock-in HD (85Q) minipigs and their wild-type sibling of different ages. We follow gene expression related to the metabolism and DNA damage repair, together with DNA damage detection by the qPCR method. To investigate gene expression changes in the putamen, we also performed transcriptome analysis by next-generation sequencing (RNAseq). Results/Outcome: A trend of increased antioxidant gene SOD2 and DNA glycosylase NEIL2 gene expression was observed in isolated knock-in HD fibroblasts. Unfortunately, there are no similar results in PBMC or DNA damage analysis. RNAseq analysis showed no significant difference in gene expression in 12-month old animals and eight significantly differentially expressed genes in 18-month old animals. Conclusions: The qPCR results suggest the earlier onset of molecular changes in the knock-in HD fibroblasts than in the PBMC. RNAseq results suggest that differences in gene expression in putamen tissues are age-dependent and appear at 18 months.