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Vitamin D and/or calcium deficient diets may differentially affect muscle fiber neuromuscular junction innervation
Authors:David J. Gifondorwa PhD  Tyran D. Thompson BS  June Wiley BS  Alexander E. Culver BS  Pamela K. Shetler AS  Guilherme V. Rocha PhD  Yanfei L. Ma MD  Venkatesh Krishnan PhD  Henry U. Bryant PhD
Affiliation:1. Eli Lilly and Company Research Laboratories, Laboratory for Experimental Medicine, Indianapolis, Indiana, USA;2. Eli Lilly and Company Research Laboratories, Cardiovascular Research, Indianapolis, Indiana, USA;3. College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, USA;4. Eli Lilly and Company Research Laboratories, Musculoskeletal Research, Indianapolis, Indiana, USA;5. Eli Lilly and Company Research Laboratories, Statistics ‐ Discovery/Development, Indianapolis, Indiana, USA
Abstract:Introduction: There is evidence that supports a role for Vitamin D (Vit. D) in muscle. The exact mechanism by which Vit. D deficiency impairs muscle strength and function is not clear. Methods: Three‐week‐old mice were fed diets with varied combinations of Vit. D and Ca2+ deficiency. Behavioral testing, genomic and protein analysis, and muscle histology were performed with a focus on neuromuscular junction (NMJ) ‐related genes. Results: Vit. D and Ca2+ deficient mice performed more poorly on given behavioral tasks than animals with Vit. D deficiency alone. Genomic and protein analysis of the soleus and tibialis anterior muscles revealed changes in several Vit. D metabolic, NMJ‐related, and protein chaperoning and refolding genes. Conclusions: These data suggest that detrimental effects of a Vit. D deficient or a Vit. D and Ca2+ deficient diet may be a result of differential alterations in the structure and function of the NMJ and a lack of a sustained stress response in muscles. Muscle Nerve 54 : 1120–1132, 2016
Keywords:calcium  muscle  neuromuscular junction  stress response  vitamin D
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