Glial fibrillary acidic protein and glutamine synthetase in subregions of prefrontal cortex in schizophrenia and mood disorder

Toro, Carla; Hallak, Jaime E. C.; Dunham, Jason S.; Deakin, Bill

doi:10.1016/j.neulet.2006.05.067

Cited by 85 publications

(73 citation statements)

References 35 publications

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“…We used a comprehensive range of measures, mRNA and protein expression of GFAP as well as classification of astrocyte morphology based on GFAP immunostaining. The measures were internally consistent with one another and confirmed previously noted correlations between GFAP expression and age (positive; Nichols et al, 1993) and tissue pH (negative; Feresten et al, 2013;Toro et al, 2006), supporting the internal validity of our study as well as the results of earlier studies.…”

Section: Discussionsupporting

confidence: 89%

Increased expression of astrocyte markers in schizophrenia: Association with neuroinflammation

Catts

Wong

Fillman

et al. 2014

Aust N Z J Psychiatry

130

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Objective: While schizophrenia may have a progressive component, the evidence for neurodegenerative processes as indicated by reactive astrocytes is inconclusive. We recently identified a subgroup of individuals with schizophrenia with increased expression of inflammatory markers in prefrontal cortex, and hypothesized that this subgroup would also have reactive astrocytes. Method:We measured glial fibrillary acidic protein (GFAP) mRNA by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) and protein levels by immunoblotting in grey matter homogenate from 37 individuals with schizophrenia and 37 unaffected controls. We examined the morphology of GFAP-positive astrocytes in immunostained sections of middle frontal gyrus. We tested if GFAP expression or astrocyte morphology were altered in people with schizophrenia with increased expression of inflammatory markers. We used RNA-Seq data on a subset of patients and controls (n=20/group) to ascertain whether mRNA transcripts associated with astrogliosis were elevated in the individuals with active neuroinflammation.Results: GFAP (mRNA and protein) levels and astrocyte morphology were not significantly different between people with schizophrenia and controls overall. However, individuals with schizophrenia with neuroinflammation had increased expression of GFAP mRNA (t(33)=2.978, p=0.005), hypertrophic astrocyte morphology (χ 2 (2)=6.281, p=0.043), and statistically significant elevated expression of three mRNA transcripts previously associated with astrogliosis. Conclusions:We found clear evidence of astrogliosis in a subset of people with schizophrenia. We suggest that the lack of astrogliosis reported in previous studies may be due to cohort differences in aetiopathology, illness stage, treatment exposure, or a failure to examine subsets of people with schizophrenia.

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Section: Discussionsupporting

confidence: 89%

Increased expression of astrocyte markers in schizophrenia: Association with neuroinflammation

Catts

Wong

Fillman

et al. 2014

Aust N Z J Psychiatry

130

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“…30 However, an increased protein expression of GFAP in lamina II, III, IV and VI in BA9 of the dlPFC has also been reported. 97 This previously reported increase in GFAP was found to correlate with antipsychotic intake; however, post hoc analysis of this in our data set did not support this finding (Spearman's rank 0.221). We consider that the reason for the inconsistency of these results may relate to the presence of GFAP on 2D gels as multiple protein spots representing post-translational modifications and/or different isoforms.…”

Section: Methodological Issuescontrasting

confidence: 76%

Prominent synaptic and metabolic abnormalities revealed by proteomic analysis of the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder

et al. 2007

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There is evidence for both similarity and distinction in the presentation and molecular characterization of schizophrenia and bipolar disorder. In this study, we characterized protein abnormalities in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder using two-dimensional gel electrophoresis. Tissue samples were obtained from 35 individuals with schizophrenia, 35 with bipolar disorder and 35 controls. Eleven protein spots in schizophrenia and 48 in bipolar disorder were found to be differentially expressed (P < 0.01) in comparison to controls, with 7 additional spots found to be altered in both diseases. Using mass spectrometry, 15 schizophrenia-associated proteins and 51 bipolar disorder-associated proteins were identified. The functional groups most affected included synaptic proteins (7 of the 15) in schizophrenia and metabolic or mitochondrial-associated proteins (25 of the 51) in bipolar disorder. Six of seven synaptic-associated proteins abnormally expressed in bipolar disorder were isoforms of the septin family, while two septin protein spots were also significantly differentially expressed in schizophrenia. This finding represented the largest number of abnormalities from one protein family. All septin protein spots were upregulated in disease in comparison to controls. This study provides further characterization of the synaptic pathology present in schizophrenia and of the metabolic dysfunction observed in bipolar disorder. In addition, our study has provided strong evidence implicating the septin protein family of proteins in psychiatric disorders for the first time.

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“…Recent reports suggest that chronic antipsychotic use (both typical and atypical) causes a 10% decrease in brain weight and does in fact decrease cortical brain volume in controlled stereological studies of non-human primates [50,51]). This volume reduction was linked to a significant reduction in astrocytes and oligodendrocytes, a finding that parallels the reduction in astrocytic and oligodendrocyte markers found in some [52][53][54][55] but not all [56,57] postmortem studies of people with schizophrenia.…”

Section: Discussionsupporting

confidence: 57%

Selection of Reference Gene Expression in a Schizophrenia Brain Cohort

Rothmond

Fung

Wong

et al. 2010

Schizophrenia Research

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Glial fibrillary acidic protein and glutamine synthetase in subregions of prefrontal cortex in schizophrenia and mood disorder

Cited by 85 publications

References 35 publications

Increased expression of astrocyte markers in schizophrenia: Association with neuroinflammation

Increased expression of astrocyte markers in schizophrenia: Association with neuroinflammation

Prominent synaptic and metabolic abnormalities revealed by proteomic analysis of the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder

Selection of Reference Gene Expression in a Schizophrenia Brain Cohort

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