Proteomic analysis reveals protein changes within layer 2 of the insular cortex in schizophrenia

Abstract

Abnormalities in the size and activity of the insular cortex (IC), a brain region involved in auditory hallucinations and language, have been previously found in brain imaging studies in schizophrenia. In addition, cortical layer 2 has been shown to be abnormal in many brain regions in schizophrenia. In this study, 2-D DIGE was used to quantitatively analyse protein expression in schizophrenia and control cases (n = 15/group) in microdissected layer 2 IC tissue. Proteomic analyses revealed 57 significantly differentially expressed (p<0.05) protein spots in schizophrenia. Validation of differential expression of two of the proteins differentially expressed was subsequently confirmed using Western blotting. This work provides evidence of abnormal protein expression in layer 2 of the IC in schizophrenia, supporting previous work of reduced neuronal size in this cortical layer in the IC. Over half of proteins abnormally expressed in this study have not been reported previously in proteomic studies investigating schizophrenia or neurodegenerative disorders. Proteins found to be abnormally expressed appear to collectively impact on neuronal plasticity through roles in neurite outgrowth, cellular morphogenesis and synaptic function.

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

“…87 Our findings therefore provide further support for a reappraisal of these disorders as distinct diagnostic entities, 32 although other evidence for the distinct character must also be considered in any such reappraisal. 32,49,88,89 In keeping with previous proteomic studies of schizophrenia and bipolar disorder, 38 including one of the hippocampus in schizophrenia, 90 our findings implicate proteins involved in cytoskeletal 42,46,90 and metabolic 42,45,46,48,58 cellular mechanisms and, specifically in bipolar disorder, cell death pathways. 91,92 The results complement findings of transcriptomic investigations in these brain regions.…”

“…57 The laser microdissector (PALM Microlaser Technologies) was used in the cut mode as previously described. 58 Areas of DG, CA4, CA2/3, and CA1 were marked on each methyl green-stained section of each slide using the PALM software, cut using laser-assisted microdissection, collected in microtubes, and stored at −80°C.…”

Schizophrenia-Like Features in Transgenic Mice Overexpressing Human HO-1 in the Astrocytic Compartment

“…The GFAP.HMOX1 mouse displays many characteristics commensurate with human schizophrenia including (1) hyperkinesias (Ungvari et al, 2009), (2) attenuated prepulse inhibition that is typically more evident in men (Aasen et al, 2005), (3) hyperdopaminergia (Meisenzahl et al, 2007;Howes and Kapur, 2009) without accelerated DA turnover (Post et al, 1975;van Kammen et al, 1986;Beuger et al, 1996), (4) diminished D 1 receptor binding [prefrontal cortex in schizophrenia (Okubo et al, 1997); nucleus accumbens in our mice], (5) increased basal ganglia serotonin levels (Korpi et al, 1986), (6) altered hippocampal cytoarchitectonics (Jakob and Beckmann, 1986;Scheibel and Conrad, 1993), (7) decreased neuronal reelin content (Knuesel, 2010), (8) increased brain ␣-synuclein expression (Pennington et al, 2008), (9) CNS oxidative stress (Prabakaran et al, 2004), (10) delayed hemodynamic responses (Ford et al, 2005), (11) altered brain sterol metabolism (Horrobin et al, 1991) (J. Hascalovici and H. M. Schipper, unpublished results), and, central to our thesis, (12) upregulation of HO-1 in affected neural tissues (Prabakaran et al, 2004), and (13) astroglial mitochondrial damage and autophagy (Prabakaran et al, 2004;Kolomeets and Uranova, 2010). The GFAP.HMOX1 mice also exhibit enhanced astroglial iron deposition (W. Song, H. Zukor, and H. M. Schipper, unpublished observations) akin to earlier observations in HMOX1-transfected glial cultures (Zukor et al, 2009).…”

Proteomics of the Synapse – A Quantitative Approach to Neuronal Plasticity

“…With the advent of quantitative proteomics using ICAT (65), iTRAQ (66), AQUA (67), SILAC (68), SILAM (69), and label-free quantification approaches (70) some of these issues have been resolved and differential proteomic profiling in combination with absolute and relative quantifications can address changes of the neuronal proteome associated with diseases (e.g. [71][72][73][74][75][76][77][78][79] or is able to tackle protein half-lives (80,81). Crucial to all of these approaches are absolute high fidelity in the technical prerequisites of the analyses including accuracy of workflows, validity of data, dynamic range of protein assessment, or PTM levels.…”