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.
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.
Objective
To determine whether vitamin D deficiency influences functional and disease outcomes in a mouse model of ALS.
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.