Presynaptic modulation of amino acid release from synaptosomes.

Using synaptosomes prepared from whole rat brain, the spontaneous, calcium-independent, and calcium-dependent release of glutamate and GABA was assessed. Time intervals of 1-30 seconds were studied. Spontaneous release of glutamate (but not GABA) was elevated by 10 microM NMDA or AMPA by thirty seconds.

Deficient NMDA-mediated glutamate release from synaptosomes of schizophrenics.

Previous studies from our laboratory indicated that the veratridine-induced release of glutamate and GABA from synaptosomes derived from brains of schizophrenics was decreased. In the present study, synaptosomes were prepared from frozen brain samples from schizophrenics and from controls. Stimulation by 10 mumol/L 2-amino-3-hydroxy-5-methoxylisoxazole-4-propionic acid (AMPA) produced equal glutamate release from both groups.

Plasma serine in schizophrenics and controls measured by gas chromatography-mass spectrometry.

In several previous studies, we reported significantly higher plasma serine concentrations in psychotic (and schizophrenic) subjects compared with nonpsychotic and control subjects. In those studies, we used a gas chromatography technique to assay the amino acids. Perry and Hanson (1985), using cation-exchange chromatography to assay plasma amino acids, found no differences in the plasma serine concentrations of controls compared with schizophrenic patients.

Evidence of glutamatergic deficiency in schizophrenia.

Studies of amino acid release were carried out using frozen sections from brains of schizophrenics and controls. Synaptosomes were prepared via differential centrifugation in Ficoll allowing the veratridine-induced release of aspartate, glutamate, glycine, and GABA to be measured. The release of glutamate and gamma-aminobutyric acid (GABA) was reduced in the synaptosomes from schizophrenics.

Abnormal serine hydroxymethyl transferase activity in the temporal lobes of schizophrenics.

We studied the kinetics of the enzyme serine hydroxymethyl transferase (SHMT) and the concentration of its metabolic substrates serine and glycine, in the postmortem brains of controls and schizophrenics. The Km of SHMT, and the concentration of serine and glycine were all significantly higher in the temporal lobes of brain tissues from schizophrenics than in those from controls. These differences were not observed in the frontal lobe specimens.