You are not logged in.

Androgen-dependent impairment of myogenesis in spinal and bulbar muscular atrophy

Malena, Adriana, Pennuto, Maria, Tezze, Caterina, Querin, Giorgia, D'Ascenzo, Carla, Silani, Vincenzo, Cenacchi, Giovanna, Scaramozza, Annarita, Romito, Silvia, Morandi, Lucia, Pegoraro, Elena, Russell, Aaron P, Sorarù, Gianni and Vergani, Lodovica 2013, Androgen-dependent impairment of myogenesis in spinal and bulbar muscular atrophy, Acta neuropathologica, vol. 126, no. 1, pp. 109-121, doi: 10.1007/s00401-013-1122-9.

Attached Files
Name Description MIMEType Size Downloads

Title Androgen-dependent impairment of myogenesis in spinal and bulbar muscular atrophy
Author(s) Malena, Adriana
Pennuto, Maria
Tezze, Caterina
Querin, Giorgia
D'Ascenzo, Carla
Silani, Vincenzo
Cenacchi, Giovanna
Scaramozza, Annarita
Romito, Silvia
Morandi, Lucia
Pegoraro, Elena
Russell, Aaron PORCID iD for Russell, Aaron P orcid.org/0000-0002-7323-9501
Sorarù, Gianni
Vergani, Lodovica
Journal name Acta neuropathologica
Volume number 126
Issue number 1
Start page 109
End page 121
Total pages 13
Publisher Springer Verlag
Place of publication Berlin, Germany
Publication date 2013-07
ISSN 0001-6322
1432-0533
Keyword(s) Adult
Analysis of Variance
Androgens
Case-Control Studies
Cell Differentiation
Cell Proliferation
Cells, Cultured
Dihydrotestosterone
Drug Interactions
Female
Humans
Hypertrophy
In Situ Nick-End Labeling
Interleukin-4
Male
Microscopy, Electron, Transmission
Middle Aged
Muscle Development
Muscle Fibers, Skeletal
Muscular Atrophy, Spinal
Myosins
Peptides
Time Factors
Young Adult
Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences
Pathology
Neurosciences & Neurology
Spinal and bulbar muscular atrophy
Androgen receptor
Myogenesis
RECESSIVE BULBOSPINAL NEURONOPATHY
SKELETAL-MUSCLE PATHOLOGY
TRANSGENIC MOUSE MODEL
KENNEDY-DISEASE
SATELLITE CELLS
RECEPTOR GENE
TESTOSTERONE REPLACEMENT
HETEROZYGOUS FEMALES
HYPOGONADAL MEN
EXPRESSION
Summary Spinal and bulbar muscular atrophy (SBMA) is an inherited neuromuscular disease caused by expansion of a polyglutamine (polyQ) tract in the androgen receptor (AR). SBMA is triggered by the interaction between polyQ-AR and its natural ligands, testosterone and dihydrotestosterone (DHT). SBMA is characterized by the loss of lower motor neurons and skeletal muscle fasciculations, weakness, and atrophy. To test the hypothesis that the interaction between polyQ-AR and androgens exerts cell-autonomous toxicity in skeletal muscle, we characterized the process of myogenesis and polyQ-AR expression in DHT-treated satellite cells obtained from SBMA patients and age-matched healthy control subjects. Treatment with androgens increased the size and number of myonuclei in myotubes from control subjects, but not from SBMA patients. Myotubes from SBMA patients had a reduced number of nuclei, suggesting impaired myotube fusion and altered contractile structures. The lack of anabolic effects of androgens on myotubes from SBMA patients was not due to defects in myoblast proliferation, differentiation or apoptosis. DHT treatment of myotubes from SBMA patients increased nuclear accumulation of polyQ-AR and decreased the expression of interleukin-4 (IL-4) when compared to myotubes from control subjects. Following DHT treatment, exposure of myotubes from SBMA patients with IL-4 treatment rescued myonuclear number and size to control levels. This supports the hypothesis that androgens alter the fusion process in SBMA myogenesis. In conclusion, these results provide evidence of an androgen-dependent impairment of myogenesis in SBMA that could contribute to disease pathogenesis.
Language eng
DOI 10.1007/s00401-013-1122-9
Field of Research 111601 Cell Physiology
1103 Clinical Sciences
1109 Neurosciences
Socio Economic Objective 920112 Neurodegenerative Disorders Related to Ageing
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2013, Springer-Verlag Berlin Heidelberg
Persistent URL http://hdl.handle.net/10536/DRO/DU:30072218

Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 18 times in TR Web of Science
Scopus Citation Count Cited 19 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 19 Abstract Views, 1 File Downloads  -  Detailed Statistics
Created: Mon, 13 Apr 2015, 22:48:58 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.