Abstract
High homocysteine (Hcy) levels, mainly caused by vitamin B12 deficiency, have been reported to induce amyloid-β (Aβ) formation and tau hyperphosphorylation in mouse models of Alzheimer’s disease. However, the relationship between B12 deficiency and Aβ aggregation is poorly understood, as is the associated mechanism. In the current study, we used the transgenic C. elegans strain GMC101, which expresses human Aβ1–42 peptides in muscle cells, to investigate the effects of B12 deficiency on Aβ aggregation–associated paralysis. C. elegans GMC101 was grown on nematode growth medium with or without B12 supplementation or with 2-O-α-D-glucopyranosyl-L-ascorbic acid (AsA-2G) supplementation. The worms were age-synchronized by hypochlorite bleaching and incubated at 20 °C. After the worms reached the young adult stage, the temperature was increased to 25 °C to induce Aβ production. Worms lacking B12 supplementation exhibited paralysis faster and more severely than those that received it. Furthermore, supplementing B12-deficient growth medium with AsA-2G rescued the paralysis phenotype. However, AsA-2G had no effect on the aggregation of Aβ peptides. Our results indicated that B12 supplementation lowered Hcy levels and alleviated Aβ toxicity, suggesting that oxidative stress caused by elevated Hcy levels is an important factor in Aβ toxicity.
Highlights
Before performing paralysis assay in this culture condition, first, fluorescence images of Pacdh-1::GFP (VL749) worms were taken to observe dietary B12 status of worms cultivated on nematode growth medium (NGM) with or without B12 supplementation (B12 + worms or B12 − worms)
The results showed a significant accumulation of Hcy and methylmalonic acid (MMA) in B12 − worms compared to that in B12 + worms (Figure 2); the Hcy and MMA levels in the B12 − worms were 2.2- and 3.6-fold higher, respectively, Antioxidants 2021, 10, x FOR PEER REVIEW
To investigate the effect of reduced reactive oxygen species (ROS) levels in B12 − GMC101 worms on paralysis
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. B12 is a water-soluble vitamin that is well known for its complex chemical structure. The B12 molecule is composed of a corrin ring with a central cobalt atom linked to dimethylbenzimidazole. B12 exists in four different chemical forms, depending on the chemical group bound to the cobalt atom. Most commercially available B12 supplements contain a cyano group and are known as cyanocobalamin. The cyano group can be replaced with adenosyl, or methyl group to form the biologically active form adenosylcobalamin (AdoCbl), or methylcobalamin (MeCbl), respectively [1]. Humans mainly acquire B12 by consuming meat, dairy products, fish, and shellfish, as plants and mushrooms do not contain substantial amounts [2]
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