Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Research Article
  • Published:

Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: a study of complexin mRNAs

Molecular Psychiatry volume 5, pages 425–432 (2000)Cite this article

Abstract

Complexin (cx) I and cx II are synaptic proteins preferentially expressed by inhibitory and excitatory hippocampal neurons respectively. We previously reported decreased hippocampal formation cx mRNA and protein expression in schizophrenia, with a greater loss of cx II than cx I. The present in situ hybridization study was both an attempt at replication, and an extension to include bipolar and unipolar mood disorders, using sections from the stanley foundation brain series. in schizophrenia, both mrnas were decreased in some hippocampal subfields, especially ca4, but were preserved in subiculum. the cx ii/cx i mrna ratio was unchanged. in bipolar disorder, the mrnas were reduced in ca4, subiculum and parahippocampal gyrus, with the deficit in subiculum being diagnostically specific. no alterations in cx mrnas were found in major depression. treatment of rats with antipsychotics (haloperidol or chlorpromazine) for 2 weeks had no effect on hippocampal cx mrnas. these data replicate the finding of decreased cx i and cx ii expression in the hippocampus in schizophrenia and show a similar or greater abnormality in bipolar disorder. non-replication of the cx ii > cx I mRNA loss in schizophrenia means that the hypothesis of a preferential involvement of excitatory connections was not supported. The results extend the emerging evidence that altered circuitry may be a component of the neuroanatomy of both schizophrenia and bipolar mood disorder.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Friston K, Frith C . Schizophrenia: a disconnection syndrome? Clin Neurosci 1995; 3: 89–97

    CAS  PubMed  Google Scholar 

  2. Andreasen NC . A unitary model of schizophrenia. Bleuler's ‘fragmented phrene’ as schizencephaly Arch Gen Psychiatry 1999; 56: 781–787

    Article  CAS  Google Scholar 

  3. Harrison PJ . The neuropathology of schizophrenia. A critical review of the data and their interpretation Brain 1999; 122: 593–624

    Article  Google Scholar 

  4. Eastwood SL, Burnet PWJ, Harrison PJ . Altered synaptophysin expression as a marker of synaptic pathology in schizophrenia Neuroscience 1995; 66: 309–319

    Article  CAS  Google Scholar 

  5. Eastwood SL, Harrison PJ . Decreased synaptophysin in the medial temporal lobe in schizophrenia demonstrated using immunoautoradiography Neuroscience 1995; 69: 339–343

    Article  CAS  Google Scholar 

  6. Young CE, Arima K, Xie J, Hu L, Beach TG, Falkai P, Honer WG . SNAP-25 deficit and hippocampal connectivity in schizophrenia Cerebr Ctx 1998; 8: 261–268

    Article  CAS  Google Scholar 

  7. Eastwood SL, Harrison PJ . Detection and quantification of hippocampal synaptophysin mRNA in schizophrenia using autoclaved formalin-fixed paraffin-embedded sections Neuroscience 1999; 93: 99–106

    Article  CAS  Google Scholar 

  8. Vawter MP, Howard AL, Hyde TM, Kleinman JE, Freed WJ . Alterations of hippocampal secreted N-CAM in bipolar disorder and synaptophysin in schizophrenia Mol Psychiatry 1999; 4: 467–475

    Article  CAS  Google Scholar 

  9. Harrison PJ, Eastwood SL . Preferential involvement of excitatory neurons in medial temporal lobe in schizophrenia Lancet 1998; 352: 1669–1673

    Article  CAS  Google Scholar 

  10. Takahashi S, Yamamoto H, Matsuda Z, Ogawa M, Yagyu K, Taniguchi T et al. Identification of two highly homologous presynaptic proteins distinctly localised at the dendritic and somatic synapses FEBS Lett 1995; 368: 455–460

    Article  CAS  Google Scholar 

  11. Ishizuka T, Saisu H, Odani S, Kumanishi T, Abe T . Distinct regional distribution in the brain of messenger RNAs for the two isoforms of synaphin associated with the docking/fusion complex Neuroscience 1999; 88: 295–306

    Article  CAS  Google Scholar 

  12. Yamada M, Saisu H, Ishizuka T, Takahashi H, Abe T . Immunohistochemical distribution of the two isoforms of synaphin/complexin involved in neurotransmitter release: localization at the distinct central nervous system regions and synaptic types Neuroscience 1999; 93: 7–18

    Article  CAS  Google Scholar 

  13. Eastwood SL, Burnet PWJ, Harrison PJ . Expression of complexin I and II mRNAs and their regulation by antipsychotic drugs in the rat forebrain Synapse (in press)

  14. Johnston NL, Cerevnak J, Shore AD, Torrey EF, Yolken RH . Multivariate analysis of RNA levels from postmortem human brains as measured by three different methods of RT-PCR J Neurosci Meth 1997; 77: 83–92

    Article  CAS  Google Scholar 

  15. Harrison PJ, Heath PR, Eastwood SL, Burnet PWJ, McDonald B, Pearson RCA . The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies:selective mRNA vulnerability and comparison with their encoded proteins Neurosci Lett 1995; 200: 151–154

    Article  CAS  Google Scholar 

  16. Burnet PWJ, Harrison PJ . Substance P (NK1) receptors in the cingulate cortex in unipolar and bipolar mood disorder and schizophrenia Biol Psychiatry 2000; 47: 80–83

    Article  CAS  Google Scholar 

  17. Honer G, Falkai P, Chen C, Arango V, Mann JJ, Dwork AJ . Synaptic and plasticity-associated proteins in anterior frontal cortex in severe mental illness Neuroscience 1999; 91: 1247–1255

    Article  CAS  Google Scholar 

  18. Eastwood SL, Cairns NJ, Harrison PJ . Synaptophysin gene expression in schizophrenia. An investigation of synaptic pathology in the cerebral cortex Br J Psychiatry 2000; 176: 236–242

    Article  CAS  Google Scholar 

  19. Harrison PJ, Burnet PWJ, Falkai P, Bogerts B, Eastwood SL . Gene expression and neuronal activity in schizophrenia: a study of polyadenylated mRNA in the hippocampal formation and cerebral cortex Schizophr Res 1997; 26: 93–102

    Article  CAS  Google Scholar 

  20. Esiri MM, Pearson RCA . Perspectives from other diseases and lesions. In: Harrison PJ, Roberts GW (eds) The Neuropathology of Schizophrenia and its Interpretation Oxford University Press: Oxford (in press)

  21. Ono S, Baux G, Sekiguchi M, Fossier P, Morel NF, Nihonmatsu I et al. Regulatory roles of complexins in neurotransmitter release from mature presynaptic nerve terminals Eur J Neurosci 1998; 10: 2143–2152

    Article  CAS  Google Scholar 

  22. Takahashi S, Ujihara H, Huang GZ, Yagyu K, Sanbo M, Kaba H et al. Reduced hippocampal LTP in mice lacking a presynaptic protein, complexin II Eur J Neurosci 1999; 11: 2359–2366

    Article  CAS  Google Scholar 

  23. Öngür D, Drevets DC, Price JL . Glial reduction in the subgenual prefrontal cortex in mood disorders Proc Natl Acad Sci USA 1998; 95: 13290–13295

    Article  Google Scholar 

  24. Rajkowska G, Miguel-Hidalgo JJ, Wei JR, Dilley G, Pittman SD, Meltzer HY et al. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression Biol Psychiatry 1999; 45: 1085–1098

    Article  CAS  Google Scholar 

  25. Benes FM, Kwok EW, Vincent SL, Todtenkopf MS . Reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic depressives Biol Psychiatry 1998; 44: 98–97

    Article  Google Scholar 

  26. Baumann B, Bogerts B . The pathomorphology of schizophrenia and mood disorders: similarities and differences Schizophr Res 1999; 39: 141–148

    Article  CAS  Google Scholar 

  27. Harrison PJ . The neuropathological effects of antipsychotic drugs Schizophr Res 1999; 40: 87–99

    Article  CAS  Google Scholar 

  28. Benes FM . Evidence for altered trisynaptic circuitry in schizophrenic hippocampus Biol Psychiatry 1999; 46: 589–599

    Article  CAS  Google Scholar 

  29. Weinberger DR . Cell biology of the hippocampal formation in schizophrenia Biol Psychiatry 1999; 45: 395–402

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Tissue was generously donated by the Stanley Foundation Brain Bank, courtesy of Drs Michael Knable, Fuller Torrey, Maree Webster and Robert Yolken. The success of the Foundation in facilitating post mortem psychosis research through this unique undertaking is gratefully acknowledged. The research was supported by a Stanley Foundation International Centre Award and a Wellcome Trust Senior Fellowship (041840) to PJH.

Author information

Authors and Affiliations

  1. Departments of Psychiatry and Clinical Neurology (Neuropathology), University of Oxford, UK

    S L Eastwood & P J Harrison

Authors
  1. S L Eastwood
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. P J Harrison
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to P J Harrison.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Eastwood, S., Harrison, P. Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: a study of complexin mRNAs. Mol Psychiatry 5, 425–432 (2000). https://doi.org/10.1038/sj.mp.4000741

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4000741

Keywords

This article is cited by

Search

Advanced search

Quick links

pFad - Phonifier reborn

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.

Note: This service is not intended for secure transactions such as banking, social media, email, or purchasing. Use at your own risk. We assume no liability whatsoever for broken pages.


Alternative Proxies:

Alternative Proxy

pFad Proxy

pFad v3 Proxy

pFad v4 Proxy