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- Title
Vitamin D<sub>3</sub> Deficiency Differentially Affects Functional and Disease Outcomes in the G93A Mouse Model of Amyotrophic Lateral Sclerosis.
- Authors
Solomon, Jesse A.; Gianforcaro, Alexandro; Hamadeh, Mazen J.
- Abstract
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 D3 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 D3 groups: 1) adequate (AI; 1 IU D3/g feed) and 2) deficient (DEF; 0.025 IU D3/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. AI mice. DEF mice reached CS 2 six days later vs. AI mice (P = 0.004), confirmed by a logrank test which revealed that DEF mice reached CS 2 at a 43% slower rate vs. AI mice (HR = 0.57; 95% CI: 0.38, 1.74; P = 0.002). Body weight-adjusted TA (AI: r = 0.662, P = 0.001; DEF: r = 0.622, P = 0.006) and quads (AI: r = 0.661, P = 0.001; DEF: r = 0.768; P<0.001) weights were strongly correlated with age at CS 2. Conclusion Vitamin D3 deficiency improves early disease severity and delays disease onset, but reduces performance in functional outcomes following disease onset, in the high-copy G93A mouse.
- Publication
PLoS ONE, 2011, Vol 6, Issue 12, p1
- ISSN
1932-6203
- Publication type
Academic Journal
- DOI
10.1371/journal.pone.0029354