Cortical expression of glial fibrillary acidic protein and glutamine synthetase is decreased in schizophrenia.
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.
Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109-2200, United States. asteffek@umich.edu
Amy E
AE
Steffek
Robert E
RE
McCullumsmith
Vahram
V
Haroutunian
James H
JH
Meador-Woodruff
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001253:Astrocytes / Q000473:pathology; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis*; D005974:Glutamate-Ammonia Ligase / Q000032:analysis*; D006179:Gyrus Cinguli / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008297:Male; D017397:Prefrontal Cortex / Q000473:pathology; D051381:Rats; D012016:Reference Values; D012559:Schizophrenia / Q000473:pathology*; D013702:Temporal Lobe / Q000473:pathology; D014793:Visual Cortex / Q000473:pathology
D005904:Glial Fibrillary Acidic Protein; D005974:Glutamate-Ammonia Ligase