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

• Published in: Molecular psychiatry Vol. 4; no. 5; pp. 467 - 475
• Main Authors: VAWTER, M. P, HOWARD, A. L, HYDE, T. M, KLEINMAN, J. E, FREED, W. J
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.09.1999
• Subjects: Actin; Actins - analysis; Actins - immunology; Adult and adolescent clinical studies; Amino Acid Sequence; Antibody Specificity; Biological and medical sciences; Bipolar disorder; Bipolar Disorder - metabolism; Blotting, Western; Cell adhesion molecules; Cerebrospinal fluid; Cytosol - chemistry; Female; Hippocampus; Hippocampus - chemistry; Hippocampus - metabolism; Hippocampus - physiopathology; Humans; Hydrogen-Ion Concentration; Immunoblotting; Male; Medical sciences; Mental disorders; Middle Aged; Molecular Sequence Data; Neural cell adhesion molecule; Neural Cell Adhesion Molecules - analysis; Neural Cell Adhesion Molecules - immunology; Neural Cell Adhesion Molecules - metabolism; Peptide Fragments - immunology; Precipitin Tests; Predictive Value of Tests; Prefrontal cortex; Proteins; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Schizophrenia; Schizophrenia - metabolism; Suicide; Synaptophysin; Synaptophysin - analysis; Synaptophysin - immunology; Synaptophysin - metabolism; Mood disorder; Human; Synaptophysin; Neural cell adhesion molecule; Pathophysiology; Postmortem; Cell adhesion molecule; Central nervous system; Schizophrenia; Bipolar disorder; Psychosis; Comparative study; Hippocampus; Brain (vertebrata)
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/sj.mp.4000547

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.