Alteration of Amino Acid Metabolism in Epileptogenic Mice by Elevation of Brain Pyridoxal Phosphate

Abstract

A single intraperitoneal injection of pyridoxal-5'-phosphate (PLP) in a species of mouse, DBA/2J, that is normally susceptible to sound-induced convulsion exacerbated its epileptic condition. The effect of injection was most pronounced about 30 min after the administration and subsided gradually within the following 4 h. Correlated with this increased seizure susceptibility were enhanced levels of synaptosomal aspartate and glutamate, and a diminished gamma-aminobutyric acid (GABA) level. The concentrations of nonneuroactive amino acids remained unchanged. When stimulated with veratrine, synaptosomes prepared from PLP-injected mice showed an increased release of aspartate and glutamate and a decreased release of GABA compared to those prepared from control mice. The activity of glutamate decarboxylase in the brains of PLP-treated mice was lowered, whereas the activity of GABA-transaminase was enhanced. Finally, the epileptic condition of DBA mice could be ameliorated by maintenance on a diet composed of vitamin B6-deficient feed and cellulose.

Diseases Associated with Defects in Vitamin B6 Metabolism or Utilization

“…Defects in vitamin B6 metabolism may contribute to some types of neurolog ical abnormalities (19, 87,89,93,119,123, for examples), because of the involvement of PLP in numerous key pathways of neural function (namely neurotransmitter synthesis, amino acid metabolism, sphingolipid biosynthe sis, and degradation) (24). Vitamin B6 deficiencies have multiple neurolog ical effects (16, 24); however, a cause-and-effect link between defective vitamin B6 metabolism and neurological disorders has not been proven.…”

Status epilepticus in a neonate treated with pyridoxine because of a familial recurrence risk for antiquitin deficiency: pyridoxine toxicity?

“…Upon intraperitoneal injection of pyridoxine, 100mg/kg, young rats developed EEG changes, and motor seizures at 250mg/kg 11 . In another study, seizures could be induced in rats by intraperitoneal injection of other B 6 vitamers such as PLP and pyridoxal 12 . Large doses of pyridoxine and PLP injected directly into cerebral ventricles provoked seizures in dogs 13 .…”

Chronological changes in pyridoxine‐5′‐phosphate oxidase immunoreactivity in the seizure‐sensitive gerbil hippocampus

“…On the other hand, excessive PLP concentration enhances seizure susceptibility by diminishing the GABA level (Norris et al, 1985), reducing GABA synthesis (Gospe et al, 1994), and modifying the GABA A receptor, leading to a degeneration of GABAergic neurotransmission (Ishioka et al, 1995). Therefore, the modulation of PNP oxidase expression may play an important role in the regulation of GAD activity or of seizure susceptibility.…”