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Vitamin D 3 supplementation at 50x the adequate intake attenuates functional decline in the transgenic G93A mouse model of amyotrophic lateral sclerosis: have females reached their threshold for toxicity?
Author(s) -
Gianforcaro Alexandro,
Solomon Jesse Adam,
Hamadeh Mazen Jamal
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.343.3
Subject(s) - amyotrophic lateral sclerosis , medicine , vitamin , animal model , toxicity , vitamin d and neurology , anesthesia , endocrinology , physiology , disease
Background We previously demonstrated that dietary vitamin D 3 (D 3 ) at 10x the adequate intake (AI) attenuates the decline in paw grip endurance (PaGE) and motor performance (MP) in the G93A mouse model of amyotrophic lateral sclerosis (ALS). Higher doses may elicit more robust changes in functional and disease outcomes. Objective To determine the effects of dietary D 3 at 50x AI on PaGE, MP, clinical score (CS), disease onset (CS2) and lifespan in the G93A mouse model of ALS. Methods At age 25 d, 51 G93A mice were provided food ad libitum with either adequate (AI; 1 IU D 3 /g feed) or high (HiD; 50 IU D 3 /g feed) D 3 . Tibialis anterior (TA), quadriceps and brain were harvested at age 113 d from an additional 35 G93A mice. Results HiD‐F had a 28% greater CS vs. AI‐F (P = 0.099). For PaGE, HiD had an 11% greater score vs. AI over time (P = 0.029), and a 32% greater score vs. AI between CS2 and endpoint (CS5; P = 0.078). For MP between CS2 and CS5, HiD‐M had a 24% greater AUC vs. AI‐M (P = 0.068). Age at CS2 significantly correlated with body weight‐adjusted TA (r = 0.61, P < 0.001) and quadriceps (r = 0.56, P < 0.001) weights. Males had a faster rate of reaching CS5 vs. females: AI (HR = 2.2, 95% CI: 1.1, 7.0; P = 0.016); HiD (HR = 1.9, 95% CI; 1.0, 4.9; P = 0.061). Conclusion Dietary D 3 at 50x the AI attenuates functional decline in the G93A mouse model of ALS. However, females may have reached the threshold for toxicity. Supported by NSERC and Faculty of Health‐York U.Grant Funding Source : NSERC and Faculty of Health‐York University