Direct Evidence that 4'-O-methylpyridoxine Induces Hyperactivity and Convulsions due to Pyridoxal Phosphate Deficiency in the Brain

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  • Direct Evidence that 4'-<i>O</i>-methylpyridoxine Induces Hyperactivity and Convulsions due to Pyridoxal Phosphate Deficiency in the Brain

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Ginkgo biloba seed (GBS) poisoning is caused by the toxic substance 4'-O-methylpyridoxine (MPN). Gammaaminobutyric acid (GABA) in the brain is suggested to be involved in the convulsion-inducing effect of MPN.<br>To clarify the direct effects of MPN in the brain on behavior and changes in vitamin B6 and GABA concentration, we intrathecally administered MPN (5-80 nmol) to mice. Some of them developed hyperactivity and seizures. Incidence of behavioral abnormalities were correlated with the MPN dose/body weight. In the analysis of the brain, mice with hyperactivity shown decreased Pyridoxal-5'-phosphate (PLP) and decreased GABA/Glutamae (Glu) ratio. Administered MPN dose/body weight was negatively correlated with PLP (p<0.001) and GABA/Glu ratio (p＝0.004) in the brain. MPN concentration in the brain negatively correlated with PLP (p<0.001) and GABA/Glu ratio (p<0.001), and a positive correlation between concentration of MPN and phosphorylated MPN (4'-O-methylpyridoxine-5'-phosphate, MPNP) was found (p＝0.01). We report for the first time that MPNP is produced from MPN in vivo and MPN decreases PLP concentrations in the brain, resulting in the decrease of GABA/Glu ratio and this change leads to behavioral changes.

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