Alterations in synaptic proteins and their encoding mRNAs in prefrontal cortex in schizophrenia: a possible neurochemical basis for ‘hypofrontality’ (original) (raw)

Molecular Psychiatry volume 4, pages 39–45 (1999)Cite this article

Abstract

An impairment of prefrontal cortical functioning in schizophrenia (‘hypofrontality’) has been suggested by clinical, neuroimaging, and postmortem brain tissue studies. We used Western immunoblot and Northern hybridization analyses of postmortem brain tissue obtained from 14 schizophrenic patients and 12 control patients of similar ages to measure tissue levels of synaptophysin (a structural synaptic vesicle protein) and of SNAP-25 (a 25-kDa presynaptic protein), and their encoding mRNAs, in Brodmann's area 10 of prefrontal cortex. There were significant decreases in tissue levels of both of these proteins in prefrontal cortex of schizophrenic patients relative to controls. In contrast, tissue levels for the mRNAs encoding these proteins were not decreased in schizophrenic patients. Subsequent labeling of the same Western immunoblots showed no difference in tissue levels of glial fibrillary acidic protein (GFAP) in schizophrenic and control patients. Similarly, subsequent hybridization of the same Northern hybridization membranes showed no difference in tissue levels of GFAP mRNA or of 28S rRNA in schizophrenic and control patients. These alterations in tissue levels of synaptophysin and SNAP-25 are consistent with the idea that the clinically observed ‘hypofrontality’ of schizophrenia arises from abnormalities of synaptic number or structural integrity in prefrontal cortex.

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Authors and Affiliations

  1. Department of Veterans' Affairs Medical Center,
    C N Karson, R E Mrak & W S T Griffin
  2. Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, Arkansas
    C N Karson & W S T Griffin
  3. Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
    R E Mrak
  4. Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas
    K O Schluterman, J G Sheng & W S T Griffin
  5. Medical Examiner's Office for the State of Arkansas, Little Rock, Arkansas, USA
    W Q Sturner
  6. Department of Neurology, Rui-Jin Hospital, Shanghai Second Medical University, Shanghai, 200025, China
    J G Sheng

Authors

  1. C N Karson
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  2. R E Mrak
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  3. K O Schluterman
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  4. W Q Sturner
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  5. J G Sheng
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  6. W S T Griffin
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Corresponding author

Correspondence toW S T Griffin.

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Karson, C., Mrak, R., Schluterman, K. et al. Alterations in synaptic proteins and their encoding mRNAs in prefrontal cortex in schizophrenia: a possible neurochemical basis for ‘hypofrontality’.Mol Psychiatry 4, 39–45 (1999). https://doi.org/10.1038/sj.mp.4000459

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