Quantitative autoradiographic analysis of glutamate binding sites in the hippocampal formation in normal and schizophrenic brain post mortem.
Using quantitative autoradiography, the anatomical distribution of the binding sites (kainate, N-methyl-D-aspartate and quisqualate) for the excitatory neurotransmitter glutamate has been established in the hippocampal formation from control and schizophrenic brains, post mortem. There is a loss of the kainate subtype particularly in schizophrenic hippocampi mainly from the CA4/CA3 mossy fibre termination zone of the cornu ammonis (CA4 and CA3; control and schizophrenic left hippocampus, respectively, 54.2 and 66.6 pmol/g; 18.3 and 17.9 pmol/g), as well as bilateral losses in the dentate gyrus (left 14.2 pmol/g and right 28.0 pmol/g; left 9.5 pmol/g and right 7.9 pmol/g, control and schizophrenic, respectively) and parahippocampal gyrus (left 50.8 pmol/g and right 41.7 pmol/g, left 27.7 pmol/g and right 25.3 pmol/g, control and schizophrenic, respectively). There is complete preservation of N-methy-D-aspartate sites in schizophrenic hippocampi, and a marginally significant loss of the quisqualate binding site in CA4/CA3 regions (left 249 fmol/g and right 306 fmol/g, left 157 fmol/g and right 148 fmol/g, control and schizophrenic, respectively). These findings reflect the possible importance of glutamate in the pathophysiology of schizophrenia and represent novel targets for therapeutic manipulation in schizophrenia.
Kerwin
R
R
Institute of Psychiatry, Department of Neuroscience, Denmark Hill, London, U.K.
Patel
S
S
Meldrum
B
B
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000328:Adult; D000368:Aged; D001345:Autoradiography; D005260:Female; D005971:Glutamates / Q000378:metabolism; D006624:Hippocampus / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007608:Kainic Acid / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016202:N-Methylaspartate / Q000378:metabolism; D011712:Pyramidal Tracts / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D011810:Quinoxalines / Q000378:metabolism; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000032:analysis* / Q000378:metabolism; D012016:Reference Values; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology; D014316:Tritium
D005971:Glutamates; D011810:Quinoxalines; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D014316:Tritium; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D007608:Kainic Acid