Dietary Vitamin D.sub.3 Restriction Exacerbates Disease Pathophysiology in the Spinal Cord of the G93A Mouse Model of Amyotrophic Lateral Sclerosis

Dietary vitamin D.sub.3 (D.sub.3) restriction reduces paw grip endurance and motor performance in G93A mice, and increases inflammation and apoptosis in the quadríceps of females. ALS, a neuromuscular disease, causes progressive degeneration of motor neurons in the brain and spinal cord. We analyzed...

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Veröffentlicht in:PloS one 2015-05, Vol.10 (5)
Hauptverfasser: Moghimi, Elnaz, Solomon, Jesse A, Gianforcaro, Alexandro, Hamadeh, Mazen J
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Sprache:eng
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Zusammenfassung:Dietary vitamin D.sub.3 (D.sub.3) restriction reduces paw grip endurance and motor performance in G93A mice, and increases inflammation and apoptosis in the quadríceps of females. ALS, a neuromuscular disease, causes progressive degeneration of motor neurons in the brain and spinal cord. We analyzed the spinal cords of G93A mice following dietary D.sub.3 restriction at 2.5% the adequate intake (AI) for oxidative damage (4-HNE, 3-NY), antioxidant enzymes (SOD2, catalase, GPx1), inflammation (TNF-[alpha], IL-6, IL-10), apoptosis (bax/bcl-2 ratio, cleaved/pro-caspase 3 ratio), neurotrophic factor (GDNF) and neuron count (ChAT, SMI-36/SMI-32 ratio). Beginning at age 25 d, 42 G93A mice were provided food ad libitum with either adequate (AI;1 IU D.sub.3 /g feed; 12 M, 11 F) or deficient (DEF; 0.025 IU D.sub.3 /g feed; 10 M, 9 F) D.sub.3 . At age 113 d, the spinal cords were analyzed for protein content. Differences were considered significant at P [less than or equal to] 0.10, since this was a pilot study. DEF mice had 16% higher 4-HNE (P = 0.056), 12% higher GPx1 (P = 0.057) and 23% higher Bax/Bcl2 ratio (P = 0.076) vs. AI. DEF females had 29% higher GPx1 (P = 0.001) and 22% higher IL-6 (P = 0.077) vs. AI females. DEF males had 23% higher 4-HNE (P = 0.066) and 18% lower SOD2 (P = 0.034) vs. AI males. DEF males had 27% lower SOD2 (P = 0.004), 17% lower GPx1 (P = 0.070), 29% lower IL-6 (P = 0.023) and 22% lower ChAT (P = 0.082) vs. DEF females. D.sub.3 deficiency exacerbates disease pathophysiology in the spinal cord of G93A mice, the exact mechanisms are sex-specific. This is in accord with our previous results in the quadriceps, as well as functional and disease outcomes.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0126355