Cortical expression of glial fibrillary acidic protein and glutamine synthetase is decreased in schizophrenia

Abstract

Altered expression of structural and functional molecules expressed by astrocytes may play a role in the pathophysiology of schizophrenia. We investigated the hypothesis that the astrocytic enzyme glutamine synthetase, involved in maintaining the glutamate-glutamine cycle, and the cytoskeletal molecule glial fibrillary acidic protein (GFAP) are abnormally expressed in schizophrenia. We used Western blot analysis to measure levels of glutamine synthetase and GFAP in several brain regions of subjects with schizophrenia and a comparison group. We found that glutamine synthetase protein expression was significantly decreased in the superior temporal gyrus, and both glutamine synthetase and GFAP were significantly reduced in the anterior cingulate cortex in schizophrenia. Neither molecule demonstrated altered expression in the dorsolateral prefrontal cortex, primary visual cortex, or hippocampus. Chronic treatment with haloperidol did not alter the expression of these molecules in the rat brain, suggesting that our findings are not due to a medication effect. These data support an astrocytic component to the pathophysiology of schizophrenia and suggest that astrocytic molecules involved in enzymatic activity and cytoskeletal integrity may have a role in disease-related abnormalities in this illness.

Selection of Reference Gene Expression in a Schizophrenia Brain Cohort

“…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.…”

Thalamic transcriptome screening in three psychiatric states

“…However, decreased glutamine synthetase in the superior temporal gyrus and anterior cingulate cortex in SZ was recently reported. 33 Over 100 insulin-responsive genes have previously been reported to be altered in SZ hippocampal neurons in a direction opposing their response to insulin, and the study of these various genes in relation to IGF1 in human neuroblastoma cells have been implicated in SZ. 34,35 These studies also show that pharmacological stimulation of muscarinic and insulin/IGF1 receptors reverse the gene expression changes in specific subsets of genes that have been dysregulated in SZ, further highlighting the importance of insulin signaling.…”

Glucocorticoid treatment of astrocytes results in temporally dynamic transcriptome regulation and astrocyte-enriched mRNA changes in vitro

“…Some single-gene diseases have been associated with specific glial alterations, e.g., Alexander's disease with astrocytes (44), myelination disorders with oligodendrocytes (23), but recent results implicate a glial component in many complex disorders as well, e.g., psychiatric disorders (reviewed in Ref. 13); schizophrenia (68,72), bipolar disorder (55), major depression (12). Changes in astrocyte density and size in distinct brain regions of the postmortem brains of patients with depression imply that distinct subpopulations of astrocytes are disrupted in the disorder (46,56).…”