期刊
PLOS ONE
卷 6, 期 12, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0029354
关键词
-
资金
- Natural Sciences and Engineering Research Council of Canada
Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by motor neuron death in the central nervous system. Vitamin D supplementation increases antioxidant activity, reduces inflammation and improves motor neuron survival. We have previously demonstrated that vitamin D-3 supplementation at 10x the adequate intake improves functional outcomes in a mouse model of ALS. Objective: To determine whether vitamin D deficiency influences functional and disease outcomes in a mouse model of ALS. Methods: At age 25 d, 102 G93A mice (56 M, 46 F) were divided into two vitamin D-3 groups: 1) adequate (Al; 1 IU D-3/g feed) and 2) deficient (DEF; 0.025 IU D-3/g feed). At age 113 d, tibialis anterior (TA), quadriceps (quads) and brain were harvested from 42 mice (22 M and 20 F), whereas the remaining 60 mice (34 M and 26 F) were followed to endpoint. Results: During disease progression, DEF mice had 25% (P = 0.022) lower paw grip endurance AUC and 19% (P = 0.017) lower motor performance AUC vs. AI mice. Prior to disease onset (CS 2), DEF mice had 36% (P = 0.016) lower clinical score (CS) vs. Al mice. DEF mice reached CS 2 six days later vs. Al mice (P = 0.004), confirmed by a logrank test which revealed that DEF mice reached CS 2 at a 43% slower rate vs. Al mice (HR = 0.57; 95% Cl: 0.38, 1.74; P = 0.002). Body weight-adjusted TA (Al: r = 0.662, P = 0.001; DEF: r = 0.622, P = 0.006) and quads (Al: r = 0.661, P = 0.001; DEF: r = 0.768; P < 0.001) weights were strongly correlated with age at CS 2. Conclusion: Vitamin D-3 deficiency improves early disease severity and delays disease onset, but reduces performance in functional outcomes following disease onset, in the high-copy G93A mouse.
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