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. Release induced by either 10 mumol/L kainic acid (KA) or n-methyl-d-asparate (NMDA) was reduced significantly in the preparations derived from schizophrenics. Similarly, the amount of GABA released by 50 mumol/L glutamate was also reduced in the schizophrenic-derived synaptosomes. However, in membranes derived from the crude synaptosomal pellet, no differences between the controls and schizophrenics were observed in measures of total glutamate binding or its displacement by NMDA. The data demonstrate a deficiency in NMDA (and possibly KA) receptor functioning schizophrenics and support the "second-generation" theories of schizophrenia as a glutamatergic deficiency disorder.
Department of Psychiatry, University of Iowa, College of Medicine, Iowa City 52242.
A D
AD
Sherman
T S
TS
Hegwood
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S
Baruah
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R
Waziri
D001921:Brain / Q000503:physiopathology*; D046508:Culture Techniques; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006801:Humans; D008297:Male; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000502:physiology; D012559:Schizophrenia / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D013574:Synaptosomes / Q000502:physiology*; D013702:Temporal Lobe / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005971:Glutamates; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid