The disruption of methionine (L-MET) metabolism has been linked with neurodevelopmental disorders such as autism and schizophrenia and neurodegenerative disorders such as Alzheimer's disorder. We previously showed that repeated administration to adult mice of methionine produced impairments of cognitive deficits. Considering the decreased neurogenesis and increased molecular inflammation hypotheses of cognitive deficits in Alzheimer's, we aimed to explore whether the methionine regimen that produced cognitive deficits is associated with altered neuroinflammation, neurogenesis, or neurodegeneration. We found that repeated administration of L-MET at a dose equivalent to two-fold of daily dietary intake for seven days enhanced the activation of microglia and inflammation in the brain, and decreased neurogenesis in the hippocampus without affecting degeneration. Furthermore, sub-chronic and chronic L-MET treatment of human neuroblastoma (SH-SY5Y) inhibited cell cycle progression, an effect that was reversed by decreasing removing L-MET from the medium. These results support a role for neuroinflammation and neurogenesis in mediating the mechanism through which L-MET induces cognitive deficits. The results also uncover L-MET restriction, neuroinflammation, and neurogenesis as potential preventive and/or therapeutic targets for mental disorders associated with cognitive disorders, including schizophrenia and Alzheimer's disease.
Keywords: Brain; Methionine; Microglia; Neurogenesis; Neuroinflammation.
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