Absence of basal ganglia amino acid neuron deficits in schizophrenia in three collections of brains.
Amino acid (glutamatergic, GABAergic) neuron deficiency theories of schizophrenia offer plausible explanations of pathogenesis. However, reports of disease-related reductions in amino acid synthesizing enzymes in post-mortem brains are contradictory. We measured neuronal uptake sites for gamma-aminobutyric acid (GABA; [3H]nipecotic acid binding) and nerve terminal/glial uptake sites for L-glutamate (D-[3H aspartate binding) in three independent groups of post-mortem brains from patients with schizophrenia and control subjects. Measurements were also made of the phencyclidine site of the glutamate N-methyl-D-aspartate (NMDA) receptor. Samples from patients showed no reductions in the binding of [3H]nipecotic acid or D-[3H]aspartate in caudate, putamen or globus pallidus. On the contrary, some increased binding of both ligands was observed in patients in many comparisons with controls. There were no clear-cut changes in NMDA receptor binding. The most consistent change in the brain sets was increased [3H]nipecotic acid binding in caudate-putamen. This could be due to neuroleptic treatment. The findings produce no evidence that schizophrenia involves major loss of GABA neuron terminals in the basal ganglia or losses of corticostriatal glutamatergic projections.
School of Biological Sciences, Neuroscience Division, University of Manchester, UK.
M D
MD
Simpson
P
P
Slater
J F
JF
Deakin
C G
CG
Gottfries
I
I
Karlsson
B
B
Grenfeldt
T J
TJ
Crow
D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000378:metabolism*; D000368:Aged; D027322:Amino Acid Transport System X-AG; D000704:Analysis of Variance; D001224:Aspartic Acid; D001479:Basal Ganglia / Q000378:metabolism*; D001665:Binding Sites; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism*; D016022:Case-Control Studies; D050485:GABA Plasma Membrane Transport Proteins; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009557:Nipecotic Acids; D027361:Organic Anion Transporters; D010622:Phencyclidine / Q000031:analogs & derivatives; D011392:Proline / Q000031:analogs & derivatives*; D011869:Radioligand Assay; D012559:Schizophrenia / Q000378:metabolism*; D014316:Tritium
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009557:Nipecotic Acids; D027361:Organic Anion Transporters; D014316:Tritium; C030278:nipecotic acid; D001224:Aspartic Acid; C012058:tenocyclidine; D011392:Proline; C010983:homoproline; D010622:Phencyclidine