Increase in HLA-DR Immunoreactive Microglia in Frontal and Temporal Cortex of Chronic Schizophrenics

• Published in: Journal of neuropathology and experimental neurology Vol. 59; no. 2; pp. 137 - 150
• Main Authors: RADEWICZ, KATRINA, GAREY, LAURENCE J, GENTLEMAN, STEPHEN M, REYNOLDS, RICHARD
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Association of Neuropathologists, Inc 01.02.2000; Lippincott Williams & Wilkins; Oxford University Press
• Subjects: Adult and adolescent clinical studies; Age Factors; Aged; Aged, 80 and over; Amyloid beta-Peptides - analysis; Antibodies; Antipsychotic Agents - therapeutic use; Astrocytes - chemistry; Astrocytes - pathology; Biological and medical sciences; Brain; Cell Count; Glial Fibrillary Acidic Protein - analysis; HLA-DR Antigens - analysis; Humans; Immunohistochemistry; Linear Models; Medical sciences; Microglia - chemistry; Microglia - drug effects; Microglia - pathology; Neurofibrillary Tangles - metabolism; Neurons; Neurophysiology; Postmortem Changes; Prefrontal Cortex - chemistry; Prefrontal Cortex - pathology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Schizophrenia; Schizophrenia - metabolism; Schizophrenia - pathology; Single-Blind Method; Temporal Lobe - chemistry; Temporal Lobe - pathology; Viral antibodies; Psychosis; Human; Immunohistochemistry; Pathology; Schizophrenia; Exploration; Temporal cortex; Frontal cortex; Brain (vertebrata); Microglia
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1093/jnen/59.2.137

Glia play a major role in neuronal migration, synapse formation, and control of neurotransmission in the developing and mature nervous system. This study investigated whether chronic schizophrenia is associated with glial changes in 3 regions of the cerebral cortexdorsolateral prefrontal cortex (Brodmannʼs area 9), the superior temporal gyrus (area 22), and the anterior cingulate gyrus (area 24). In a blind study, astroglia and microglia were identified immunocytochemically in frozen sections from postmortem schizophrenic and control brains. Astroglia and microglia were identified using antibodies to glial fibrillary acidic protein (GFAP) and class II human leucocyte antigen (HLA-DR) respectively. They were then quantified for each cortical layer. Significant differences were found in HLA-DR microglial numerical density in 2 of the areas. A 28% increase (p < 0.05) was found in area 9 in 8 schizophrenics (115 ± 9 cells/mm) compared with 10 controls (89 ± 5 cells/mm), when combining all cortical layers and both cerebral hemispheres. For area 22, there was a 57% increase (p < 0.01) in microglia in 7 schizophrenics (139 ± 6 cells/mm) compared with 10 controls (88 ± 5 cells/mm). In area 24 the same trend was evident, but the results did not reach significance. Microglial number was further analyzed for each cortical layer, which confirmed the overall pattern. For all areas, numerical density of astroglia showed no significant differences between schizophrenics and controls. Cortical thickness was measured in all areas and total neuronal numerical density was estimated for area 22. Again, no significant differences were found between schizophrenics and controls. This study demonstrates a specific increase in the numerical density of HLA-DR microglia in temporal and frontal cortex of chronic schizophrenics, not related to aging, which might be implicated in possible changes in cortical neuropil architecture in schizophrenia.