RETRACTED: Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in the postmortem frontal cortex from schizophrenia patients

Abstract

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-1β, tumor necrosis factor-α, 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 A2 and cyclooxygenase were significantly elevated in postmortem brains from SZ patients. 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.

Microglial Gene Expression Alterations in the Brains of Patients with Psychiatric Disorders

“…HLA-DR-positive microglia in the posterior hippocampus are increased in paranoid schizophrenia patients compared with patients who have residual schizophrenia or with controls [31]. A significant increase was observed in the mean protein CD11b levels in the frontal cortex of patients with schizophrenia compared with controls [27]. CD11b is one of the most important phagocyte receptors for recognizing microbial pathogens [35], and it has been found in murine [36,37] and human microglia [38]; furthermore, it is widely used as a marker for microglial identification.…”

“…The protein expression levels of M1-related nuclear transcription factor subunits, NF-Bp50 and NF-Bp65, were significantly increased in the frontal cortices of schizophrenia patients. In contrast, the protein and mRNA levels of the M2-related growth factor BDNF were significantly reduced in the frontal cortices of schizophrenia patients [27]. The protein expression levels of other microglial marker chemokines, S100A8/A9, were significantly higher in the dorsolateral prefrontal cortices of patients with schizophrenia [42].…”

“…In frontal cortex samples from SZ patients, the IL-1␤ protein level was significantly increased [27], whereas IL-1 receptor antagonist (IL-1RA) protein, which is mostly enriched in the prefrontal cortex, was significantly reduced in the schizophrenic brain samples [66]. The IL-6 and IL-8 mRNA expression levels were also significantly upregulated in the dorsolateral prefrontal cortices from schizophrenic patients [29].…”

“…The IL-6 and IL-8 mRNA expression levels were also significantly upregulated in the dorsolateral prefrontal cortices from schizophrenic patients [29]. The TNF␣ mRNA and protein levels were also significantly increased in frontal cortex samples from schizophrenic patients [27]. Additionally, the TNF receptor type I (TNFR1) mRNA level was significantly increased in both the anterior cingulate and dorsolateral prefrontal cortices of patients with schizophrenia [67].…”

“…For example, HLA-DR-positive (i.e., activated) microglia are found in patients with lateonset schizophrenia (age older than 40 years) [20]. HLA-DR-positive microglia are increased in the frontal cortex [27][28][29][30] and temporal cortex [5,6] of patients with chronic schizophrenia, while the brain region morphologies are not drastically altered in general [28]. HLA-DR-positive microglia in the posterior hippocampus are increased in paranoid schizophrenia patients compared with patients who have residual schizophrenia or with controls [31].…”