Vitamin B12 deficiency results in severe oxidative stress, leading to memory retention impairment in Caenorhabditis elegans

Abstract

Oxidative stress is implicated in various human diseases and conditions, such as a neurodegeneration, which is the major symptom of vitamin B₁₂ deficiency, although the underlying disease mechanisms associated with vitamin B₁₂ deficiency are poorly understood. Vitamin B₁₂ deficiency was found to significantly increase cellular H₂O₂ and NO content in Caenorhabditis elegans and significantly decrease low molecular antioxidant [reduced glutathione (GSH) and L-ascorbic acid] levels and antioxidant enzyme (superoxide dismutase and catalase) activities, indicating that vitamin B₁₂ deficiency induces severe oxidative stress leading to oxidative damage of various cellular components in worms. An NaCl chemotaxis associative learning assay indicated that vitamin B₁₂ deficiency did not affect learning ability but impaired memory retention ability, which decreased to approximately 58% of the control value. When worms were treated with 1mmol/L GSH, L-ascorbic acid, or vitamin E for three generations during vitamin B₁₂ deficiency, cellular malondialdehyde content as an index of oxidative stress decreased to the control level, but the impairment of memory retention ability was not completely reversed (up to approximately 50%). These results suggest that memory retention impairment formed during vitamin B₁₂ deficiency is partially attributable to oxidative stress.

Keywords: Caenorhabditis elegans; Cobalamin; Homocysteine; Methionine synthase; Oxidative stress; Vitamin B(12).