Muscular atrophy - page 4 Scientific Publications

Latest publication 01/30/2020

Polyglutamine-Expanded Androgen Receptor Alteration of Skeletal Muscle Homeostas

Polyglutamine (polyQ) expansions in the androgen receptor (AR) gene cause spinal and bulbar muscular atrophy (SBMA), a neuromuscular disease...

Array
(
    [id_prestablog_news] => 1216
    [id_shop] => 1
    [date] => 2020-01-30 00:00:00
    [date_modification] => 2024-02-09 14:15:12
    [langues] => ["1","2"]
    [actif] => 1
    [slide] => 0
    [url_redirect] => 
    [average_rating] => 
    [number_rating] => 
    [author_id] => 1
    [featured] => 0
    [prim_key] => 2389
    [id_lang] => 1
    [title] => Polyglutamine-Expanded Androgen Receptor Alteration of Skeletal Muscle Homeostas
    [paragraph] => Polyglutamine-Expanded Androgen Receptor Alteration of Skeletal Muscle Homeostasis and Myonuclear Aggregation Are Affected by Sex, Age and Muscle Metabolism
    [content] => 
Authors
M Chivet, C Marchioretti, M Pirazzini, D Piol

 Lab
University of Padova, Padova, Italy
Journal
Cells
Abstract
Polyglutamine (polyQ) expansions in the androgen receptor (AR) gene cause spinal and bulbar muscular atrophy (SBMA), a neuromuscular disease characterized by lower motor neuron (MN) loss and skeletal muscle atrophy, with an unknown mechanism. We generated new mouse models of SBMA for constitutive and inducible expression of mutant AR and performed biochemical, histological and functional analyses of phenotype. We show that polyQ-expanded AR causes motor dysfunction, premature death, IIb-to-IIa/IIx fiber-type change, glycolytic-to-oxidative fiber-type switching, upregulation of atrogenes and autophagy genes and mitochondrial dysfunction in skeletal muscle, together with signs of muscle denervation at late stage of disease. PolyQ expansions in the AR resulted in nuclear enrichment. Within the nucleus, mutant AR formed 2% sodium dodecyl sulfate (SDS)-resistant aggregates and inclusion bodies in myofibers, but not spinal cord and brainstem, in a process exacerbated by age and sex. Finally, we found that two-week induction of expression of polyQ-expanded AR in adult mice was sufficient to cause premature death, body weight loss and muscle atrophy, but not aggregation, metabolic alterations, motor coordination and fiber-type switch, indicating that expression of the disease protein in the adulthood is sufficient to recapitulate several, but not all SBMA manifestations in mice. These results imply that chronic expression of polyQ-expanded AR, i.e. during development and prepuberty, is key to induce the full SBMA muscle pathology observed in patients. Our data support a model whereby chronic expression of polyQ-expanded AR triggers muscle atrophy through toxic (neomorphic) gain of function mechanisms distinct from normal (hypermorphic) gain of function mechanisms.
BIOSEB Instruments Used
Grip strength test (BIO-GS3)
    [meta_description] => 
    [meta_keywords] => http://scholar.google.fr/scholar_url?url=https://www.mdpi.com/2073-4409/9/2/325/pdf&hl=fr&sa=X&d=8860860870433323443&scisig=AAGBfm0XVN3XDf8Z2lcL50SEHvvjDkfU1g&nossl=1&oi=scholaralrt&hist=dLa5yvYAAAAJ:2499066874814899551:AAGBfm05gyG2UrcKAn4A3z5Ug-ZKBR4IDw
    [meta_title] => 
    [link_rewrite] => polyglutamine-expanded-androgen-receptor-alteration-of-skeletal-muscle-homeostasis-and-myonuclear-aggregation-are-affected-by-sex--age-and-muscle-metabolism
    [actif_langue] => 1
    [read] => 1143
    [count_comments] => 0
    [id] => 1216
    [categories] => Array
        (
            [65] => Array
                (
                    [id_prestablog_categorie] => 65
                    [title] => Muscular atrophy
                    [link_rewrite] => atrophie
                )

            [20] => Array
                (
                    [id_prestablog_categorie] => 20
                    [title] => Muscular system
                    [link_rewrite] => Muscular-system
                )

            [2] => Array
                (
                    [id_prestablog_categorie] => 2
                    [title] => Publications
                    [link_rewrite] => publications
                )

        )

    [authors] => 
    [paragraph_crop] => Polyglutamine-Expanded Androgen Receptor Alteration of Skeletal Muscle Homeostasis and [...]
    [link_for_unique] => 1
    [products_liaison] => Array
        (
            [48] => Array
                (
                    [name] => Grip strength test
                    [description_short] => 
An easy way to objectively quantify the muscular strength of mice and rats, and to assess the effect of drugs, toxins, muscular (i.e. myopathy) and neurodegenerative diseases on muscular degeneration. It is widely used in conjunction with the ROTAROD motor coordination test: a normally coordinated rodent will show a decreased latency to fall off the rotating rod if its muscular strength is low. The Grip Strength Test is a must for your research on activity, motor control & coordination, and is particularly well suited for studies on Parkinson's & Huntington's disease.
New features GS4 - 2023: Color display with permanent backlight screen for easier reading, reset by footswitch, Improved battery time, Larger data memory of 500 values, Animal counter, USB port (charging/data transfer)

                    [thumb] => 
                    [img_empty] => /var/www/vhosts/de3310.ispfr.net/preprod.bioseb.com/modules/prestablog/views/img/product_link_white.jpg
                    [image_presente] => 1
                    [link] => https://preprod.bioseb.com/en/activity-motor-control-coordination/48-grip-strength-test.html
                )

        )

)
1