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


CONCLUSIONS
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.
School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, Ontario, Canada.
Jesse A
JA
Solomon
Alexandro
A
Gianforcaro
Mazen J
MJ
Hamadeh
D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000473:pathology* / Q000628:therapy; D000818:Animals; D002762:Cholecalciferol / Q000172:deficiency*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D016133:Polymerase Chain Reaction; D016896:Treatment Outcome; D014808:Vitamin D Deficiency / Q000150:complications*
D002762:Cholecalciferol