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Synaptic proteome changes in schizophrenia and bipolar disorder

ABSTRACT: Synaptic dysfunction has been implicated in the pathogenesis of schizophrenia (SCZ) and bipolar disorder (BP). In this study, we used quantitative mass-spectrometry to carry out deep and unbiased profiling of the proteome of synapses purified from the dorsolateral prefrontal cortex of 35 controls and 35 cases each with SCZ or BP. Compared to controls, SCZ and BP synapses showed substantial and similar proteomic alterations. Network and gene set enrichment analyses revealed upregulation of proteins associated with autophagy and certain vesicle transport pathways, and downregulation of proteins related to synaptic, mitochondrial, and ribosomal function in the synapses of individuals with SCZ or BP. We also uncovered evidence for dysregulation of some of the same pathways (e.g., upregulation of vesicle transport, downregulation of mitochondrial and ribosomal proteins) in the synaptic proteome of mutant mice deficient in Akap11, a recently discovered risk gene for both SCZ and BP. Our work provides novel biological insights and hypotheses into molecular dysfunction at the synapse in SCZ and BP and serves as a resource for understanding the pathophysiology of these debilitating neuropsychiatric disorders.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (ncbitaxon:9606) Mus Musculus (ncbitaxon:10090)

SUBMITTER: Steven A. Carr

PROVIDER: MSV000090320 | MassIVE |

REPOSITORIES: MassIVE

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