Disease Affects Bdnf Expression in Synaptic and Extrasynaptic Regions of Skeletal Muscle of Three SBMA Mouse Models

International Journal of Molecular Sciences

Masahisa Katsuno¹  Gen Sobue¹  Hiroaki Adachi²  AndrewP. Lieberman³  SamirR. Nath³  Katherine Halievski⁴  S.Marc Breedlove⁴  CynthiaL. Jordan⁴ 

[1] Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan;Department of Neurology, University of Occupational and Environment Health School of Medicine, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu Fukuoka 807-8555, Japan;Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA;Neuroscience Program, 108 Giltner Hall, Michigan State University, East Lansing, MI 48824-1115, USA;

关键词: SBMA;    synaptic;    extrasynaptic;    gene expression;    neurotrophic factors;    muscle;   

DOI  :  10.3390/ijms20061314

来源: DOAJ

【 摘 要 】

Spinal bulbar muscular atrophy (SBMA) is a slowly progressive, androgen-dependent neuromuscular disease in men that is characterized by both muscle and synaptic dysfunction. Because gene expression in muscle is heterogeneous, with synaptic myonuclei expressing genes that regulate synaptic function and extrasynaptic myonuclei expressing genes to regulate contractile function, we used quantitative PCR to compare gene expression in these two domains of muscle from three different mouse models of SBMA: the “97Q” model that ubiquitously expresses mutant human androgen receptor (AR), the 113Q knock-in (KI) model that expresses humanized mouse AR with an expanded glutamine tract, and the “myogenic” model that overexpresses wild-type rat AR only in skeletal muscle. We were particularly interested in neurotrophic factors because of their role in maintaining neuromuscular function via effects on both muscle and synaptic function, and their implicated role in SBMA. We confirmed previous reports of the enriched expression of select genes (e.g., the acetylcholine receptor) in the synaptic region of muscle, and are the first to report the synaptic enrichment of others (e.g., glial cell line-derived neurotrophic factor). Interestingly, all three models displayed comparably dysregulated expression of most genes examined in both the synaptic and extrasynaptic domains of muscle, with only modest differences between regions and models. These findings of comprehensive gene dysregulation in muscle support the emerging view that skeletal muscle may be a prime therapeutic target for restoring function of both muscles and motoneurons in SBMA.

【 授权许可】

Unknown