دورية أكاديمية
High-Throughput Sequencing of BACHD Mice Reveals Upregulation of Neuroprotective miRNAs at the Pre-Symptomatic Stage of Huntington's Disease.
العنوان: | High-Throughput Sequencing of BACHD Mice Reveals Upregulation of Neuroprotective miRNAs at the Pre-Symptomatic Stage of Huntington's Disease. |
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المؤلفون: | Olmo IG; Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, Belo Horizonte, Brazil., Olmo RP; Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, Belo Horizonte, Brazil.; CNRS UPR9022, Inserm U1257, Institut de Biologie Moléculaire et Cellulaire, Université de Strasbourg, Strasbourg, France., Gonçalves ANA; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, Universidade de São Paulo, São Paulo, Brazil., Pires RGW; Department of Physiological Sciences, Center for Health Sciences, Universidade Federal do Espirito Santo, Vitoria, Brazil., Marques JT; Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, Belo Horizonte, Brazil.; CNRS UPR9022, Inserm U1257, Institut de Biologie Moléculaire et Cellulaire, Université de Strasbourg, Strasbourg, France., Ribeiro FM; Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, Belo Horizonte, Brazil. |
المصدر: | ASN neuro [ASN Neuro] 2021 Jan-Dec; Vol. 13, pp. 17590914211009857. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Sage Country of Publication: United States NLM ID: 101507115 Publication Model: Print Cited Medium: Internet ISSN: 1759-0914 (Electronic) Linking ISSN: 17590914 NLM ISO Abbreviation: ASN Neuro Subsets: MEDLINE |
أسماء مطبوعة: | Publication: <2014-> : Thousand Oaks, CA : Sage Original Publication: [London] : Portland Press, 2009- |
مواضيع طبية MeSH: | Prodromal Symptoms*, High-Throughput Nucleotide Sequencing/*methods , Huntington Disease/*genetics , MicroRNAs/*biosynthesis , MicroRNAs/*genetics , Neuroprotection/*physiology, Animals ; Cells, Cultured ; Female ; Huntington Disease/metabolism ; Huntington Disease/prevention & control ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Sequence Analysis, RNA/methods ; Up-Regulation/physiology |
مستخلص: | Huntington's disease (HD) is a genetic disorder marked by transcriptional alterations that result in neuronal impairment and death. MicroRNAs (miRNAs) are non-coding RNAs involved in post-transcriptional regulation and fine-tuning of gene expression. Several studies identified altered miRNA expression in HD and other neurodegenerative diseases, however their roles in early stages of HD remain elusive. Here, we deep-sequenced miRNAs from the striatum of the HD mouse model, BACHD, at the age of 2 and 8 months, representing the pre-symptomatic and symptomatic stages of the disease. Our results show that 44 and 26 miRNAs were differentially expressed in 2- and 8-month-old BACHD mice, respectively, as compared to wild-type controls. Over-representation analysis suggested that miRNAs up-regulated in 2-month-old mice control the expression of genes crucial for PI3K-Akt and mTOR cell signaling pathways. Conversely, miRNAs regulating genes involved in neuronal disorders were down-regulated in 2-month-old BACHD mice. Interestingly, primary striatal neurons treated with anti-miRs targeting two up-regulated miRNAs, miR-449c-5p and miR-146b-5p, showed higher levels of cell death. Therefore, our results suggest that the miRNAs altered in 2-month-old BACHD mice regulate genes involved in the promotion of cell survival. Notably, over-representation suggested that targets of differentially expressed miRNAs at the age of 8 months were not significantly enriched for the same pathways. Together, our data shed light on the role of miRNAs in the initial stages of HD, suggesting a neuroprotective role as an attempt to maintain or reestablish cellular homeostasis. |
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فهرسة مساهمة: | Keywords: BACHD; Huntington’s disease; miR-146b-5p; miR-449c-5p; microRNA; pre-symptomatic stage |
المشرفين على المادة: | 0 (MIRN149 microRNA, mouse) 0 (MicroRNAs) 0 (Mirn146 microRNA, mouse) |
تواريخ الأحداث: | Date Created: 20210428 Date Completed: 20211130 Latest Revision: 20220101 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC8718118 |
DOI: | 10.1177/17590914211009857 |
PMID: | 33906482 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1759-0914 |
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DOI: | 10.1177/17590914211009857 |