Improvement of Folic Acid on the Toxicity of TAR DNA-binding Protein 43 (TDP-43) in Amyotrophic Lateral Sclerosis Caenorhabditis elegans
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Abstract:
To investigate the effect of folic acid supplementation on amyotrophic lateral sclerosis (ALS) caused by the toxicity of TAR DNA-binding protein 43 (TDP-43), the transgenic Caenorhabditis elegans (C. elegans) transformed into human TDP-43 was selected as a model organism. The lifespan, reproductive capacity, paralysis rate, head thrash frequency, feeding ability and learning and memory capacity of nematodes were evaluated after exposure to different concentrations of folic acid (0.01 mmol/L, 0.025 mmol/L, 0.05 mmol/L). The results showed that, compared with the control group, the lifespan of the nematodes in the 0.025 mmol/L group and the 0.05 mmol/L group increased by 22.48% and 11.92%, respectively. The reproductive capacity of the 0.025 mmol/L group increased by 25.26%. The paralysis rate of nematodes in 0.01 mmol/L group and 0.025 mmol/L group decreased by 20.19% and 37.62%, respectively. The frequency of head thrash in the 0.025 mmol/L group increased by 17.14%, 32.88% and 39.18% on the 2nd, 4th and 6th day after folic acid intervention, respectively. The feeding ability of the three intervention groups increased by 24.58%, 60.30% and 15.85%, respectively, and the learning and memory ability also increased by 36.84%, 57.89% and 31.58%, respectively. The above data were statistically significant (p<0.05). Compared with the 0.01 mmol/L group and the 0.05 mmol/L group, the paralysis rate of the 0.025 mmol/L group decreased significantly (p<0.05), and other indexes increased significantly (p<0.05). The results showed that folic acid supplementation could improve the toxic effects caused by hTDP-43 protein in ALS nematodes, and folic acid at the concentration of 0.025 mmol/L might be the optimal intervention dose for ALS nematodes.
