Dietary vitamin D₃ restriction differentially alters quadriceps contractile proteins in both sexes in the transgenic G93A mouse model of amyotrophic lateral sclerosis: a pilot study

Abstract

BackgroundWe previously demonstrated that dietary vitamin D3 (D3) restriction hastened the decline in functional outcomes following disease onset in the G93A mouse model of amyotrophic lateral sclerosis (ALS). ALS is a fatal neuromuscular disease characterized by motor neuron death, muscle weakness and progressive paralysis.ObjectiveIn this pilot study, we investigated the effects of dietary D3 at 2.5% the adequate intake (AI) in G93A mice on quadriceps contractile proteins (α‐actin; troponin C, trop C), inflammation (IL‐6), cell stress response (Hsp70), mitochondrial efficiency (UCP3) and apoptosis (CASP3 cleaved/pro ratio), mechanisms contributing to ALS pathology.MethodsStarting at age 25 d, 42 G93A mice were provided food ad libitum with either adequate (AI; 1 IU D3/g feed; 12 M, 11 F) or deficient (DEF; 0.025 IU D3/g feed; 10 M, 9 F) D3. Differences in quadriceps protein content were considered significant at P ≤ 0.10.ResultsIn males, DEF had 34% lower α‐actin (P = 0.096) and 38% higher trop C (P = 0.031) vs AI. In females, DEF had 32% lower trop C vs AI (P = 0.020). DEF males had 16% higher UCP3 (P = 0.093) and 57% higher trop C vs DEF females (P = 0.021).ConclusionDietary D3 restriction differentially alters markers of muscle contractile proteins in both sexes in G39A mice, which may explain the associated decline in functional capacity. (Supported by NSERC and Faculty of Health‐York U).Grant Funding Source : Supported by NSERC and Faculty of Health‐York U