The Neuroproteomics of Schizophrenia

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

“…Generally, in 2D-DIGE experiments, there remains some uncertainty whether the identification by mass spectrometry of differentially expressed gel spots is accurate in all cases, because each spot on the polyacrylamide gel theoretically could contain a multitude of proteins. In this context it is encouraging that we had overlapping results between the pH 4-7 and pH 6-11 experiments, and that results of this study are generally in line with previously identified proteins and pathways in psychotic disorders (English et al, 2011). Additionally, several findings of the pH 4-7 study could be confirmed using alternative techniques such as Western blotting, ELISA, and dot-blotting (Focking et al, 2011b).…”

“…Several previous transcriptomic and proteomic analyses have identified alterations in 14-3-3 protein isoforms in postmortem tissue of people with schizophrenia and bipolar disorder (Altar et al, 2009;English et al, 2011), and genetic association with these disorders has been reported (Grover et al, 2009;Jia et al, 2004;Wong et al, 2005). Mice lacking the isoform 14-3-3ζ display significant deficits in hippocampus-dependent functions such as working memory, sensory gating, and associative learning (Cheah et al, 2012;Qiao et al, 2014) and these changes are associated with decreased levels of NMDA receptors in the postsynaptic density (PSD) of CA1 pyramidal neurons, leading to deficits in hippocampal long-term synaptic plasticity (Qiao et al, 2014).…”

“…Proteomic studies of the brain can provide insights into the molecular mechanisms underlying psychotic disorders. In schizophrenia, systematic review and analysis of published studies indicates converging molecular pathways in various brain areas and across grey and white matter in schizophrenia, including glucose metabolism, mitochondrial function, and cytoskeletal and synaptic integrity (English et al, 2011).…”

Postmortem Brain: An Underutilized Substrate for Studying Severe Mental Illness

“…In addition, some approaches, such as chromatin-immunoprecipitation (ChIP), require large quantities of tissues from each subject (Huang et al, 2006). One approach to get around this issue has been pooling of samples; pooled samples are assayed and help generate specific hypotheses that may be tested with smaller quantities of tissue (English et al, 2009;English et al, 2011;Pennington et al, 2008). One area of postmortem proteomic research that lags behind transcript studies is the assessment of protein quality.…”

Common Proteomic Changes in the Hippocampus in Schizophrenia and Bipolar Disorder and Particular Evidence for Involvement of Cornu Ammonis Regions 2 and 3

“…37 Usingproteomicmethods, it is possible to assess global differential protein expression between disease and control states and to obtain novel insights into disease (for reviews, see the articles by English etal, 38 Görgetal, 39 andTannuandHemby 40 ).Proteomicstudies of postmortem brain tissue from subjects with schizophrenia and from subjects with bipolar disorder have focused largely on the dorsolateral prefrontal cortex [41][42][43][44][45][46][47][48][49] and the anterior cingulate cortex. [50][51][52][53] They have demonstrated alterations in cytoskeletal, synaptic, metabolic, and mitochondrial proteins.…”