Alterations of hippocampal secreted N-CAM in bipolar disorder and synaptophysin in schizophrenia.
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.
Vawter
M P
MP
NIDA-IRP, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Howard
A L
AL
Hyde
T M
TM
Kleinman
J E
JE
Freed
W J
WJ
D000199:Actins / Q000032:analysis / Q000276:immunology; D000595:Amino Acid Sequence; D000918:Antibody Specificity; D001714:Bipolar Disorder / Q000378:metabolism*; D015153:Blotting, Western; D003600:Cytosol / Q000737:chemistry; D005260:Female; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D019006:Neural Cell Adhesion Molecules / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology; D011233:Precipitin Tests; D011237:Predictive Value of Tests; D012559:Schizophrenia / Q000378:metabolism*; D013405:Suicide; D016708:Synaptophysin / Q000032:analysis / Q000276:immunology / Q000378:metabolism*
D000199:Actins; D019006:Neural Cell Adhesion Molecules; D010446:Peptide Fragments; D016708:Synaptophysin