Glial fibrillary acidic protein and glutamine synthetase in subregions of prefrontal cortex in schizophrenia and mood disorder.
Several theories of schizophrenia suggest dysfunction in glutamate neurotransmission in higher brain regions such as the prefrontal cortex (PFC). Previous studies have investigated whether astroglial abnormalities could give rise to glutamate dysfunction using glial fibrillary acidic protein (GFAP) immunocytochemistry. We have used quantitative immunoautoradiography to measure glutamine synthetase (GS), the glial enzyme which recycles synaptic glutamate, as a more direct test of glial mechanisms of abnormal glutamate function in schizophrenia. We compared GS with GFAP immunoautoradiography in dorsolateral (area 9) and orbitofrontal (area 11/47) cortex. Optical density measures from film autoradiographs revealed an increase in GFAP immunoreactivity in area 9 in schizophrenia and a decrease in area 11/47 in both schizophrenia and bipolar disorder. The increase in GFAP in area 9 significantly correlated with lifetime antipsychotic drug treatment, whereas the reduction in area 11/47 occurred despite this effect. There were no changes in GS immunoreactivity in any psychiatric disorder. Regional and antigen-specific down-regulation of GFAP protein in OFC in schizophrenia and bipolar disorder may relate to disease mechanisms of psychosis.
Toro
Carla T
CT
Neuroscience and Psychiatry Unit, University of Manchester, Manchester, UK. carla.t.toro@manchester.ac.uk
Hallak
Jaime E C
JE
Dunham
Jason S
JS
Deakin
John F W
JF
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001345:Autoradiography; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D005904:Glial Fibrillary Acidic Protein; D005974:Glutamate-Ammonia Ligase