Proteomic pathway analysis of the hippocampus in schizophrenia and bipolar affective disorder implicates 14-3-3 signaling, aryl hydrocarbon receptor signaling, and glucose metabolism: potential roles in GABAergic interneuron pathology.
14-3-3 Proteins, Adult, Bipolar Disorder, Female, Glucose, Hippocampus, Humans, Interneurons, Male, Middle Aged, Protein Interaction Maps, Proteomics, Receptors, Aryl Hydrocarbon, Schizophrenia, Signal Transduction, Young Adult, gamma-Aminobutyric Acid
Molecular Medicine Ireland (MMI) supported K. Oliver Schubert with a Clinician Scientist Fellowship which included salary and funding for equipment and materials used in this study. The Health Research Board (HRB) supported David R. Cotter with a Clinician Scientist Award (D.R.C.) which included salary and funding for equipment and materials used in this study.
Neuropathological changes of the hippocampus have been associated with psychotic disorders such as schizophrenia and bipolar disorder. Recent work has particularly implicated hippocampal GABAergic interneurons in the pathophysiology of these diseases. However, the molecular mechanisms underlying structural and cellular hippocampal pathology remain poorly understood. We used data from comprehensive difference-in-gel electrophoresis (2-D DIGE) investigations of postmortem human hippocampus of people with schizophrenia and bipolar disorder, covering the acidic (isoelectric point (pI) between pH4 and 7) and, separately, the basic (pI between pH6 and 11) sub-proteome, for Ingenuity Pathway Analysis (IPA) of implicated protein networks and pathways. Comparing disease and control cases, we identified 58 unique differentially expressed proteins in schizophrenia, and 70 differentially expressed proteins in bipolar disorder, using mass spectrometry. IPA implicated, most prominently, 14-3-3 and aryl hydrocarbon receptor signaling in schizophrenia, and gluconeogenesis/glycolysis in bipolar disorder. Both disorders were characterized by alterations of proteins involved in the oxidative stress response, mitochondrial function, and protein-endocytosis, -trafficking, -degradation, and -ubiquitination. These findings are interpreted with a focus on GABAergic interneuron pathology in the hippocampus.
Medicine and Health Sciences | Psychiatry and Psychology
Schubert KO, Föcking M, Cotter DR. Proteomic pathway analysis of the hippocampus in schizophrenia and bipolar affective disorder implicates 14-3-3 signaling, aryl hydrocarbon receptor signaling, and glucose metabolism: potential roles in GABAergic interneuron pathology. Schizophrenia Research. 2015;167(1-3):64-72
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