Effects of a CRF2R agonist and exercise on mdx and wildtype skeletal muscle.
Corticotrophin-releasing factor 2 receptor (CRF2R) agonists prevent muscle atrophy due to immobilization, denervation, and corticosteroid-induced muscle atrophy in wildtype mice. We hypothesized that a CRF2R agonist will increase skeletal muscle mass in mdx mice. Mdx (C57BL/10ScSn-Dmd(mdx)) and wildtype (C57BL/6) mice were divided into four groups: sedentary placebo, sedentary CRF2R agonist, exercised placebo, and exercised CRF2R agonist. Mice exercised on a treadmill twice weekly for 30 min (8-12 m/min, 8 weeks). Muscle and heart weights, serum creatine kinase, and gamma-glutamyltransferase activities were measured. The CRF2R agonist increased extensor digitorum longus and soleus muscle weights (P < 0.05) in wildtype and mdx mice. Sedentary mdx CRF2R and exercised mdx placebo mice had lower serum creatine kinase activity than sedentary mdx placebo mice. CRF2R-treated mice had decreased heart weights compared to placebo-treated mice. We conclude that CRF2R agonists should be further evaluated as a potential therapy for dystrophinopathies.
Hall
Julie E
JE
Department of Pediatrics, Rm. 2H18, McMaster University Medical Center, 1200 Main Street W., Hamilton, Ontario L8N 3Z5, Canada.
Kaczor
Jan J
JJ
Hettinga
Bart P
BP
Isfort
Robert J
RJ
Tarnopolsky
Mark A
MA
D000818:Animals; D001835:Body Weight; D003402:Creatine Kinase / Q000097:blood; D006321:Heart / Q000033:anatomy & histology; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000737:chemistry / Q000187:drug effects*; D009929:Organ Size; D010805:Physical Conditioning, Animal; D011506:Proteins / Q000032:analysis; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists*; D005723:gamma-Glutamyltransferase / Q000097:blood
C101531:CRF receptor type 2; D011506:Proteins; D018019:Receptors, Corticotropin-Releasing Hormone; D005723:gamma-Glutamyltransferase; D003402:Creatine Kinase