Effects of Vitamin B<sub>12</sub> Deficiency on Amyloid-β Toxicity in <i>Caenorhabditis elegans</i>
High homocysteine (Hcy) levels, mainly caused by vitamin B<sub>12</sub> deficiency, have been reported to induce amyloid-β (Aβ) formation and tau hyperphosphorylation in mouse models of Alzheimer’s disease. However, the relationship between B<sub>12</sub> deficiency and Aβ ag...
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MDPI AG
2021-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/6/962 |
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| author | Arif Andra Shoko Tanigawa Tomohiro Bito Atsushi Ishihara Fumio Watanabe Yukinori Yabuta |
| author_facet | Arif Andra Shoko Tanigawa Tomohiro Bito Atsushi Ishihara Fumio Watanabe Yukinori Yabuta |
| author_sort | Arif Andra |
| collection | DOAJ |
| description | High homocysteine (Hcy) levels, mainly caused by vitamin B<sub>12</sub> deficiency, have been reported to induce amyloid-β (Aβ) formation and tau hyperphosphorylation in mouse models of Alzheimer’s disease. However, the relationship between B<sub>12</sub> deficiency and Aβ aggregation is poorly understood, as is the associated mechanism. In the current study, we used the transgenic <i>C. elegans</i> strain GMC101, which expresses human Aβ<sub>1–42</sub> peptides in muscle cells, to investigate the effects of B<sub>12</sub> deficiency on Aβ aggregation–associated paralysis. <i>C. elegans</i> GMC101 was grown on nematode growth medium with or without B<sub>12</sub> supplementation or with 2-<i>O</i>-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 B<sub>12</sub> supplementation exhibited paralysis faster and more severely than those that received it. Furthermore, supplementing B<sub>12</sub>-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 B<sub>12</sub> supplementation lowered Hcy levels and alleviated Aβ toxicity, suggesting that oxidative stress caused by elevated Hcy levels is an important factor in Aβ toxicity. |
| first_indexed | 2024-03-10T10:23:44Z |
| format | Article |
| id | doaj.art-afef86b192f3459f866966de161a686a |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T10:23:44Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-afef86b192f3459f866966de161a686a2023-11-22T00:14:22ZengMDPI AGAntioxidants2076-39212021-06-0110696210.3390/antiox10060962Effects of Vitamin B<sub>12</sub> Deficiency on Amyloid-β Toxicity in <i>Caenorhabditis elegans</i>Arif Andra0Shoko Tanigawa1Tomohiro Bito2Atsushi Ishihara3Fumio Watanabe4Yukinori Yabuta5Department of Agricultural Science, Graduate School of Sustainability Science, Tottori University, 4-101 Koyama-Minami, Tottori 680-8553, JapanDepartment of Agricultural Science, Graduate School of Sustainability Science, Tottori University, 4-101 Koyama-Minami, Tottori 680-8553, JapanDepartment of Agricultural Science, Graduate School of Sustainability Science, Tottori University, 4-101 Koyama-Minami, Tottori 680-8553, JapanDepartment of Agricultural Science, Graduate School of Sustainability Science, Tottori University, 4-101 Koyama-Minami, Tottori 680-8553, JapanDepartment of Agricultural Science, Graduate School of Sustainability Science, Tottori University, 4-101 Koyama-Minami, Tottori 680-8553, JapanDepartment of Agricultural Science, Graduate School of Sustainability Science, Tottori University, 4-101 Koyama-Minami, Tottori 680-8553, JapanHigh homocysteine (Hcy) levels, mainly caused by vitamin B<sub>12</sub> deficiency, have been reported to induce amyloid-β (Aβ) formation and tau hyperphosphorylation in mouse models of Alzheimer’s disease. However, the relationship between B<sub>12</sub> deficiency and Aβ aggregation is poorly understood, as is the associated mechanism. In the current study, we used the transgenic <i>C. elegans</i> strain GMC101, which expresses human Aβ<sub>1–42</sub> peptides in muscle cells, to investigate the effects of B<sub>12</sub> deficiency on Aβ aggregation–associated paralysis. <i>C. elegans</i> GMC101 was grown on nematode growth medium with or without B<sub>12</sub> supplementation or with 2-<i>O</i>-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 B<sub>12</sub> supplementation exhibited paralysis faster and more severely than those that received it. Furthermore, supplementing B<sub>12</sub>-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 B<sub>12</sub> supplementation lowered Hcy levels and alleviated Aβ toxicity, suggesting that oxidative stress caused by elevated Hcy levels is an important factor in Aβ toxicity.https://www.mdpi.com/2076-3921/10/6/962Alzheimer’s diseaseamyloid-β<i>Caenorhabditis elegans</i>oxidative stressreactive oxygen speciesvitamin B<sub>12</sub> |
| spellingShingle | Arif Andra Shoko Tanigawa Tomohiro Bito Atsushi Ishihara Fumio Watanabe Yukinori Yabuta Effects of Vitamin B<sub>12</sub> Deficiency on Amyloid-β Toxicity in <i>Caenorhabditis elegans</i> Antioxidants Alzheimer’s disease amyloid-β <i>Caenorhabditis elegans</i> oxidative stress reactive oxygen species vitamin B<sub>12</sub> |
| title | Effects of Vitamin B<sub>12</sub> Deficiency on Amyloid-β Toxicity in <i>Caenorhabditis elegans</i> |
| title_full | Effects of Vitamin B<sub>12</sub> Deficiency on Amyloid-β Toxicity in <i>Caenorhabditis elegans</i> |
| title_fullStr | Effects of Vitamin B<sub>12</sub> Deficiency on Amyloid-β Toxicity in <i>Caenorhabditis elegans</i> |
| title_full_unstemmed | Effects of Vitamin B<sub>12</sub> Deficiency on Amyloid-β Toxicity in <i>Caenorhabditis elegans</i> |
| title_short | Effects of Vitamin B<sub>12</sub> Deficiency on Amyloid-β Toxicity in <i>Caenorhabditis elegans</i> |
| title_sort | effects of vitamin b sub 12 sub deficiency on amyloid β toxicity in i caenorhabditis elegans i |
| topic | Alzheimer’s disease amyloid-β <i>Caenorhabditis elegans</i> oxidative stress reactive oxygen species vitamin B<sub>12</sub> |
| url | https://www.mdpi.com/2076-3921/10/6/962 |
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