Quantitative autoradiographic analysis of glutamate binding sites in the hippocampal formation in normal and schizophrenic brain post mortem

https://doi.org/10.1016/0306-4522(90)90219-TGet rights and content

Abstract

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.

Reference (46)

  • RepresaA. et al.

    Kainate binding sites in the hippocampal mossy fibres: localization and plasticity

    Neuroscience

    (1987)
  • RobertsG.W. et al.

    Is there gliosis in schizophrenia? Investigation in the temporal lobe

    Biol. Psychiat.

    (1987)
  • TremblayE. et al.

    Autoradiographic localization of kainic acid binding sites in the human hippocampus

    Brain Res.

    (1985)
  • AltschulerL. et al.

    Hippocampal pyramidal cell orientation in schizophrenia

    Arch. Gen. Psychiat.

    (1987)
  • BogertsB. et al.

    Basal ganglia and limbic system pathology in schizophrenia. A morphometric study of brain volume and shrinkage

    Arch. Gen. Psychiat.

    (1985)
  • BrownR. et al.

    Postmortem evidence of structural brain changes in schizophrenia: differences in brain weight; temporal horn area and parahippocampal gyrus compared with affective disorder

    Arch. Gen. Psychiat.

    (1988)
  • CampsM. et al.

    Dopamine receptors in human brain: autoradiographic distribution of D2 sites

    Neuroscience

    (1989)
  • ColterN. et al.

    White matter reduction in the parahippocampal gyrus of patients with schizophrenia

    Arch. Gen. Psychiat.

    (1987)
  • CrowT.J.

    The dopamine hypothesis survives: but there must be a way ahead

    Br. J. Psychiat.

    (1987)
  • DeakinJ.F.W. et al.

    Frontal cortical and left temporal glutamatergic dysfunction in schizophrenia

    J. Neurochem.

    (1989)
  • FalkaiP. et al.

    Cell loss in the hippocampus of schizophrenics

    Eur. Arch. Psychiat. Neurol. Sci.

    (1986)
  • FonnumF.

    Glutamate: a neurotransmitter in mammalian brain

    J. Neurochem.

    (1984)
  • Flor-HenryP.

    Commentary and synthesis

  • Cited by (0)

    View full text