Alterations of hippocampal secreted N-CAM in bipolar disorder and synaptophysin in schizophrenia

M. P. Vawter, A. L. Howard, T. M. Hyde, J. E. Kleinman, W. J. Freed

Research output: Contribution to journalArticlepeer-review

Abstract

Schizophrenia and bipolar disorder have both been linked to structural abnormalities of the hippocampus, which is consistent with a neurodevelopmental anomaly. One isoform of the neural cell adhesion molecule (N-CAM) protein, cytosolic N-CAM 105-115 kDa, was previously shown to be increased in schizophrenia in the hippocampus and prefrontal cortex. Another isoform of N-CAM, the variable alternative spliced exon of N-CAM, was also increased in the hippocampus and prefrontal cortex of bipolar disorder patients. In the present study, the secreted isoform of N-CAM (SEC N-CAM), synaptophysin, and actin proteins were measured in the hippocampus of controls, suicide victims, and patients with bipolar disorder or schizophrenia by quantitative Western immunoblotting. Previous measurements of cytosolic N-CAM (105-115 kDa) protein, from the same hippocampus samples, were used to calculate the N-CAM (105-115 kDa)/synaptophysin ratio. An affinity purified antibody to SEC N-CAM recognized SEC N-CAM (108 kDa and 115 kDa) in brain but SEC N-CAM was not detectable in CSF. In bipolar disorder, but not in schizophrenia, an increased SEC N-CAM 115 kDa/108 kDa ratio was found as compared to controls (P = 0.03). The synaptophysin/actin ratio was significantly decreased in schizophrenia (P = 0.014) as compared to controls. The cytosolic N-CAM 105-115 kDa/synaptophysin ratio was increased in patients with schizophrenia (P = 0.017), but not in bipolar disorder. Thus, bipolar disorder patients show altered expression of SEC N-CAM in the hippocampus. Patients with schizophrenia show a decrease in synaptophysin and an increase in the cytosolic N-CAM 105-115 kDa/synaptophysin ratio. The results offer further evidence of differences in protein expression between bipolar disorder and schizophrenia in the hippocampus, which is consistent with a distinct neuropathology for each neuropsychiatric disorder.

Original languageEnglish (US)
Pages (from-to)467-475
Number of pages9
JournalMolecular psychiatry
Volume4
Issue number5
DOIs
StatePublished - 1999
Externally publishedYes

Keywords

  • Actin
  • Bipolar disorder
  • Hippocampus
  • Neural cell adhesion molecule
  • Schizophrenia
  • Secreted exon
  • Suicide
  • Synaptophysin
  • Western immunoblot

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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