Journal
SCHIZOPHRENIA RESEARCH
Volume 147, Issue 1, Pages 24-31Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.schres.2013.02.017
Keywords
Schizophrenia; Arachidonic acid cascade; Cytokines; Inflammation; Synaptophysin; Drebrin; Brain; Synapse
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Funding
- Intramural Research Program of the National Institute on Aging, National Institutes of Health
- PHS grant [R24MH068855]
- Intramural Research Program of the National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
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Schizophrenia (SZ) is a progressive, neuropsychiatric disorder associated with cognitive impairment. A number of brain alterations have been linked to cognitive impairment, including neuroinflammation, excitotoxicity, increased arachidonic acid (AA) signaling and reduced synaptic protein. On this basis, we tested the hypothesis that SZ pathology is associated with these pathological brain changes. To do this, we examined postmortem frontal cortex from 10 SZ patients and 10 controls and measured protein and mRNA levels of cytokines, and astroglial, microglial, neuroinflammatory, excitotoxic, AA cascade, apoptotic and synaptic markers. Mean protein and mRNA levels of interleukin-1 beta, tumor necrosis factor-alpha, glial acidic fibrillary protein (GFAP), a microglial marker CD11b, and nuclear factor kappa B subunits were significantly increased in SZ compared with control brain. Protein and mRNA levels of cytosolic and secretory phospholipase A(2) and cyclooxygenase also were significantly elevated. N-methyl-D-aspartate receptor subunits 1 and 2B, inducible nitric oxide synthase and c-Fos were not significantly different. In addition, reduced protein and mRNA levels of brain-derived neurotrophic factor, synaptophysin and drebrin were found in SZ compared with control frontal cortex. Increased neuroinflammation and AA cascade enzyme markers with synaptic protein loss could promote disease progression and cognitive defects in SZ patients. Drugs that downregulate these changes might be considered for new therapies in SZ. Published by Elsevier B.V.
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