| 1 | Biol. Psychiatry 2015 Jun 77: 959-68 |
|---|---|
| PMID | 25433904 |
| Title | Altered glutamate protein co-expression network topology linked to spine loss in the auditory cortex of schizophrenia. |
| Abstract | Impaired glutamatergic signaling is believed to underlie auditory cortex pyramidal neuron dendritic spine loss and auditory symptoms inschizophrenia. Manyschizophreniarisk loci converge on the synaptic glutamate signaling network. We therefore hypothesized that alterations in glutamate signaling protein expression and co-expression network features are present inschizophrenia. 灰质匀浆是prepared from auditory cortex gray matter of 22schizophreniaand 23 matched control subjects, a subset of whom had been previously assessed for dendritic spine density. One hundred fifty-five selected synaptic proteins were quantified by targeted mass spectrometry. Protein co-expression networks were constructed using weighted gene co-expression network analysis. Proteins with evidence for altered expression inschizophreniawere significantly enriched for glutamate signaling pathway proteins (GRIA4, GRIA3, ATP1A3, andGNAQ). Synaptic protein co-expression was significantly decreased inschizophreniawith the exception of a small group of postsynaptic density proteins, whose co-expression increased and inversely correlated with spine density inschizophreniasubjects. We observed alterations in the expression of glutamate signaling pathway proteins. Among these, the novel observation of reduced ATP1A3 expression is supported by strong genetic evidence indicating it may contribute to psychosis and cognitive impairment phenotypes. The observations of altered protein network topology further highlight the complexity of glutamate signaling network pathology inschizophreniaand provide a framework for evaluating future experiments to model the contribution of genetic risk to disease pathology. |
| SCZ Keywords | schizophrenia |