A diet deficient in vitamin D 3 delays disease onset in the female, but not the male, G93A mouse model of amyotrophic lateral sclerosis

Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by muscle weakness, paralysis and death. Prenatal vitamin D 3 (D 3 ) deficiency delays disease onset and decreases disease severity in a mouse model of multiple sclerosis, a disease which shares common pathophysiologies with ALS. Objective To determine whether a diet deficient in D 3 affects disease severity, functional outcomes and lifespan in a mouse model of ALS. Methods At age 25 d, 51 G93A mice (28 M, 23 F) were divided into two D 3 groups: 1) adequate (AI; 1 IU D 3 /g feed) and 2) deficient (DEF; 0.025 IU D 3 /g feed). Starting at age 60 d, functional and disease outcomes were measured until endpoint (CS 5). Tibialis anterior (TA), quadriceps and brain were harvested at age 113 d from an additional 35 G93A mice. Results No differences were found in disease severity and lifespan between DEF and AI mice, however DEF‐F tended to have 22% lower motor performance (MP) area under the curve vs. AI‐F between disease onset (CS 2) and CS 5 (P = 0.100). DEF‐F reached CS 2 at a 48% slower rate than AI‐F (HR = 0.52, 95% CI: 0.20, 0.89; P = 0.023), a delay of 5 d (P = 0.060). Body weight‐adjusted TA (r = 0.65, P < 0.001) and quadriceps (r = 0.66, P < 0.001) weights strongly correlated with age at CS 2. Conclusion D 3 deficiency in female G93A mice delays disease onset, but compromises MP between disease onset and endpoint. Supported by NSERC and Faculty of Health‐York U.Grant Funding Source : NSERC and Faculty of Health‐York University