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PLoS One. 2011;6(12):e29354. doi: 10.1371/journal.pone.0029354. Epub 2011 Dec 27.

Vitamin D3 deficiency differentially affects functional and disease outcomes in the G93A mouse model of amyotrophic lateral sclerosis.

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  • 1School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, Ontario, Canada.

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 D(3) supplementation at 10× 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 (AI; 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. 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= .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 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.

© 2011 Solomon et al.

PMID:
22216257
[PubMed - indexed for MEDLINE]
PMCID:
PMC3246470
Free PMC Article
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