|Many studies in recent years suggest that schizophrenia is a synaptic disease that crucially involves a reduced function of synaptic glutamate receptor signaling. However, at present it is unclear how these pathological processes are reflected in the protein content of the synapse.
In a cooperative effort together with the Psychiatry Dept. of the Magdeburg University and with a Proteomics lab in Amsterdam Leibniz neurobiologist Michael Kreutz and his team employed two-dimensional protein gel electrophoresis and mass spectrometry to characterize and compare the synaptic proteomes of the human left dorsolateral prefrontal cortex in chronic schizophrenia and of the cerebral cortex of rats treated subchronically with ketamine.
They found 35 protein spots upregulated in the synaptic proteomes of human schizophrenics compared to controls. One of these molecules, prohibitin, was also found upregulated in the rat ketamine model.
Prohibitin-overexpressing cells show aberrant spine and dendrite morphology. Thus, prohibitin could be a new potential marker for the synaptic pathology of schizophrenia and might be causally involved in the disease process.
These findings are published in the September issue of "Molecular Psychiatry"*.
*Original publication: Smalla et al., Mol Psychiatry 13: 878-896, 2008.