Elsevier

Neuroscience

Volume 78, Issue 1, 27 February 1997, Pages 99-110
Neuroscience

Cingulate cortex synaptic terminal proteins and neural cell adhesion molecule in schizophrenia

https://doi.org/10.1016/S0306-4522(96)00489-7Get rights and content

Abstract

The neuronal organization and patterns of afferent innervation are abnormal in the cingulate cortex in schizophrenia, and associated changes in synaptic terminals could be present. A panel of monoclonal antibodies was defined with biochemical and fusion protein studies as detecting syntaxin (antibody SP6), synaptophysin (antibody SP4) and synaptosomal-associated protein-25 (antibody SP12). These antibodies and a polyclonal antibody reactive with neural cell adhesion molecule were used to investigate the cingulate cortex in schizophrenia. Immunocytochemistry indicated that syntaxin immunoreactivity had a considerably wider distribution than synaptophysin. Overall, multivariate analysis indicated increased synaptic terminal protein immunoreactivity in schizophrenia compared to controls (P=0.004). Controlled for age and post mortem interval, syntaxin immunoreactivity was significantly elevated in schizophrenia (P=0.004), and neural cell adhesion molecule immunoreactivity was also elevated (P=0.05). The neural cell adhesion molecule to synaptophysin ratio was increased (P=0.005), possibly indicating the presence of less mature synapses in schizophrenia.

Elevated syntaxin immunoreactivity is consistent with increased glutamatergic afferents to the cingulate cortex in schizophrenia, and combined with the neural cell adhesion molecule to synaptophysin ratio results suggests that synaptic function in this region in schizophrenia may be abnormal.

Section snippets

Subjects and controls

Frozen samples of the cingulate cortex were available from 18 schizophrenic patients (seven males and 11 females) and 24 controls (19 males and five females). The mean age of schizophrenic patients (49.4 years, S.D. 15.7) did not differ from controls (47.3 years, S.D. 19.1), nor did mean post mortem interval (schizophrenia 14.9 h, S.D. 9.6; controls 18.0 h, S.D. 11.5). Toxicology reports were available for 16 schizophrenic patients, antipsychotic drugs were detected in seven and an additional case

Antigen characterization

The results of previous preliminary characterization studies indicated that members of the SP series of monoclonal antibodies detected synaptophysin, SNAP-25 and syntaxin. As shown in Fig. 1A, SP15 and SP17 both recognized 40 000 mol. wt proteins in CHO cells expressing synaptophysin, but not in the untransformed parent CHO cell line. Virtually identical results were obtained with the SY38 anti-synaptophysin antibody. The mobility of the synaptophysin band in CHO cells was reduced (40 000)

Discussion

The present results confirmed the reactivity of members of a panel of monoclonal antibodies with the presynaptic terminal proteins synaptophysin, SNAP-25 and syntaxin. Syntaxin immunoreactivity in the cingulate cortex in schizophrenia was increased, and the distribution of syntaxin in human cingulate cortex was much wider than that of synaptophysin. The ratio of N-CAM to synaptophysin immunoreactivity was studied as a possible marker of synaptic maturity. This ratio was significantly increased

Conclusions

Syntaxin immunoreactivity in the cingulate cortex from schizophrenics is increased, along with N-CAM and the N-CAM to synaptophysin ratio. These data are consistent with reported increases in glutamatergic afferents to the cingulate cortex in schizophrenia, and suggest the hypothesis that there may be functional impairments in neurotransmission in this region as well. Combined investigation of multiple synaptic proteins in other brain regions in schizophrenia may also be of value. In future

Acknowledgements

This work was supported by the Medical Research Council of Canada (W.G.H. and W.S.T.), the Stanley Foundation and NARSAD (W.G.H.), and the Alzheimer's Association of Ontario (W.S.T.). The authors thank Dr R. H. Scheller for pGEX–syntaxin constructs and Dr M. C. Wilson for SNAP-25. Dr B. A. Cunningham provided the antibody to N-CAM. The support and encouragement of Drs P. Davies, J. E. Kleinman, M. F. Casanova, J. Stevens, Mr M. Zito and Ms J. Gleeson is appreciated.

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