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miR155 regulation of behavior, neuropathology, and cortical transcriptomics in Alzheimer's disease

التفاصيل البيبلوغرافية
العنوان: miR155 regulation of behavior, neuropathology, and cortical transcriptomics in Alzheimer's disease
المؤلفون: Jean-Vianney Haure-Mirande, Ben Readhead, Joel T. Dudley, Soong H. Kim, Michelle E. Ehrlich, Mickael Audrain, Diego Mastroeni, Tomas Fanutza, Sam Gandy, Robert D. Blitzer
المصدر: Acta Neuropathol
بيانات النشر: Springer Science and Business Media LLC, 2020.
سنة النشر: 2020
مصطلحات موضوعية: 0301 basic medicine, Traumatic brain injury, Mice, Transgenic, Plaque, Amyloid, Neuropathology, Disease, Biology, Article, Pathology and Forensic Medicine, Pathogenesis, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Alzheimer Disease, microRNA, PSEN1, medicine, Animals, Humans, Gene Regulatory Networks, Amyotrophic lateral sclerosis, Amyloid beta-Peptides, Innate immune system, Brain, medicine.disease, Disease Models, Animal, MicroRNAs, 030104 developmental biology, Neurology (clinical), Nervous System Diseases, Transcriptome, Neuroscience, 030217 neurology & neurosurgery
الوصف: MicroRNAs are recognized as important regulators of many facets of physiological brain function while also being implicated in the pathogenesis of several neurological disorders. Dysregulation of miR155 is widely reported across a variety of neurodegenerative conditions, including Alzheimer’s disease (AD), Parkinson’s disease, amyotrophic lateral sclerosis, and traumatic brain injury. In previous work, we observed that experimentally validated miR155 gene targets were consistently enriched among genes identified as differentially expressed across multiple brain tissue and disease contexts. In particular, we found that human herpesvirus-6A (HHV-6A) suppressed miR155, recapitulating reports of miR155 inhibition by HHV-6A in infected T-cells, thyrocytes, and natural killer cells. In earlier studies, we also reported the effects of constitutive deletion of miR155 on accelerating the accumulation of Aß deposits in 4-month-old APP/PSEN1 mice. Herein, we complete the cumulative characterization of transcriptomic, electrophysiological, neuropathological, and learning behavior profiles from 4-, 8- and 10-month-old WT and APP/PSEN1 mice in the absence or presence of miR155. We also integrated human post-mortem brain RNA-sequences from four independent AD consortium studies, together comprising 928 samples collected from six brain regions. We report that gene expression perturbations associated with miR155 deletion in mouse cortex are in aggregate observed to be concordant with AD-associated changes across these independent human late-onset AD (LOAD) data sets, supporting the relevance of our findings to human disease. LOAD has recently been formulated as the clinicopathological manifestation of a multiplex of genetic underpinnings and pathophysiological mechanisms. Our accumulated data are consistent with such a formulation, indicating that miR155 may be uniquely positioned at the intersection of at least four components of this LOAD “multiplex”: (i) innate immune response pathways; (ii) viral response gene networks; (iii) synaptic pathology; and (iv) proamyloidogenic pathways involving the amyloid β peptide (Aß).
تدمد: 1432-0533
0001-6322
DOI: 10.1007/s00401-020-02185-z
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::85ecdb5c12f03753598f25cb3255691b
https://doi.org/10.1007/s00401-020-02185-z
Rights: OPEN
رقم الانضمام: edsair.doi.dedup.....85ecdb5c12f03753598f25cb3255691b
قاعدة البيانات: OpenAIRE
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