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Vitamin D 3 supplementation at 50x the adequate intake attenuates disease pathophysiology in the spinal cord of male, but is toxic in female, G93A mouse model of amyotrophic lateral sclerosis (ALS)
Author(s) -
Moghimi Elnaz,
Thampinathan Sanjeef,
Solomon Jesse,
Gianforcaro Alexandro,
Hamadeh Mazen
Publication year - 2015
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.29.1_supplement.755.15
Subject(s) - medicine , pathophysiology , endocrinology , spinal cord , amyotrophic lateral sclerosis , disease , psychiatry
Background Vitamin D 3 (D 3 ) at 50x the adequate intake (AI) improves paw grip endurance in G93A mice. However, quadriceps apoptosis increases in females, indicating a threshold of toxicity. ALS is a neuromuscular disease characterized by progressive degeneration of upper and lower motor neurons. Objective We analyzed the spinal cords of G93A mice following dietary D 3 supplementation at 50x the AI for oxidative damage (4‐HNE, 3‐NY), antioxidant enzymes (SOD2, catalase, GPx1), inflammation (TNF‐α, IL‐6, IL‐10), apoptosis (bax/bcl‐2 ratio, CASP3 cleaved/pro ratio), neurotrophic factor (GDNF), and neuron count (ChAT, SMI36/32 ratio). Methods: Beginning at age 25 d, 41 G93A mice were provided food ad libitum with either adequate (AI; 1 IU D 3 /g feed; 12 M, 11 F) or high (HiD; 50 IU D 3 /g feed; 10 M, 8 F) D 3 . At age 113 d, the spinal cords were analyzed for protein content. Differences were considered significant at P 蠄 0.05. Results: HiD females had 14% higher 3‐NY (P = 0.065), 21% lower catalase (P < 0.0001), 21% higher TNF‐ α (P = 0.003), 13% lower IL‐10 (P = 0.042), 13% higher CASP3 (P = 0.010) and 18% lower ChAT (P = 0.024) vs. AI. HiD males had 16% lower 3‐NY (P = 0.073), 24% lower IL‐6 (P = 0.085), 26% lower CASP3 (P = 0.009) and 19% lower SMI36/32 (P = 0.098) vs. AI. Conclusion In G93A mice, dietary D 3 at 50x AI is toxic in the spinal cord of females but attenuates disease pathophysiology in males. This is in accord with results in the quadriceps , as well as functional and disease severity outcomes. Future studies need to identify the sex‐specific therapeutic dose of D 3 for ALS. Grant Funding Source : NSERC, Faculty of Health‐York U.