Hyperhomocysteinemia has been considered a risk factor for neuropsychiatric disorders, but the mechanisms involved in this process have not been completely elucidated. The aim of this study was to analyze the influence of
hyperhomocysteinemia induction by
methionine supplementation considering different levels and periods of exposure in mice. For this purpose,
methionine supplementation at concentrations of 0.5 and 1% were administered in water to increase
homocysteinemia in male C57BL/6 mice, and was maintained for 3 time periods (2, 4 and 6 months of treatment). The results from one-
carbon metabolism parameters,
brain-derived neurotrophic factor (
BDNF) concentrations and behavioral evaluation were compared. The 0.5% supplementation was efficient in increasing plasma
homocysteine levels after 2 and 6 months. The 1% supplementation, increased plasma
homocysteine after 2, 4 and 6 months. Little influence was observed in
cysteine and
glutathione concentrations. Frontal cortex
BDNF levels showed a lack of treatment influence in all periods; only the expected decrease due to increasing age was observed. Moreover, the only behavioral alteration observed using a novel object recognition task was that which was expected with increasing age. We found that responses to
hyperhomocysteinemia varied based on how it was reached, and the length of toxicity. Moreover,
hyperhomocysteinemia can affect the normal pattern of one
carbon metabolism during age increase in mice. These findings allow the establishment of a reliable animal model for studies in this field.