Comparison of glutamate and gamma-aminobutyric acid uptake binding sites in frontal and temporal lobes in schizophrenia.
BACKGROUND
Theories of schizophrenia proposing deficiencies of amino acid [glutamate, gamma-aminobutyric acid (GABA)] neurons are in accord with the observed temporal lobe pathology of the disease rather than with the newer theory of glutamate hyperinnervation and hyperfunction in areas of prefrontal cortex. This study addresses the issue by measuring specific uptake sites as indices of glutamatergic and GABAergic neuron densities in frontal and temporal lobes.


METHODS
Frontal cortex (six areas) and temporal lobe (six areas of cortex, amygdala, and hippocampus) were dissected from 19 control autopsy brains and 12 brains from neuroleptic drug-treated schizophrenic patients. Groups had similar ages, postmortem intervals, and storage times. Membranes, prepared from tissue homogenates, were incubated with D-[3H]aspartate to measure neuronal and glial glutamate uptake site binding in 14 areas and with [3H]nipecotic acid to measure neuronal GABA uptake site binding in 11 areas.


RESULTS
Glutamate and GABA uptake sites were not reduced in prefrontal and temporal areas. Instead, we found small increases in glutamate uptake sites in prefrontal areas. Some tendency toward increased GABA uptake sites were not disease-related.


CONCLUSIONS
Our findings concur with other studies that propose locally overabundant glutamate systems in prefrontal cortex in schizophrenia. Losses of amino acid neurons do not accompany the temporal lobe pathology.
Simpson
M D
MD
School of Biological Sciences, Neuroscience Division, University of Manchester, United Kingdom.
Slater
P
P
Deakin
J F
JF
D000368:Aged; D001224:Aspartic Acid / Q000378:metabolism; D002908:Chronic Disease; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009557:Nipecotic Acids / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives*; D018079:Receptors, GABA / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism*
D009557:Nipecotic Acids; D018079:Receptors, GABA; D017470:Receptors, Glutamate; C030278:nipecotic acid; D001224:Aspartic Acid; D011392:Proline; C010983:homoproline