Calprotectin in microglia from frontal cortex is up‐regulated in schizophrenia: evidence for an inflammatory process?

Abstract

Schizophrenia is associated with a number of pathological changes, including alterations in levels of specific proteins. Calprotectin is a novel 36 kDa calcium-binding protein of the S100 family and appears to be a nonspecific marker of inflammation. Calprotectin has not previously been investigated in brain tissue. Samples of post-mortem brain tissue from Brodmann area 9 were obtained from prefrontal cortex from subjects with schizophrenia, bipolar affective disorder, major depression, and from controls. Calprotectin levels were determined by ELISA. To determine cellular localization, immunocytochemical and fluorescent double-labelling analyses were performed. Exogenous calprotectin was added to retinoic acid-differentiated human SH-SY5Y neuroblastoma cell cultures in order to investigate mechanisms of action of calprotectin. Calprotectin was detectable in all samples, and mean levels were noted to be highest in schizophrenic brains (P < 0.05) and lowest in controls. Levels were intermediate in bipolar affective disorder and major depression. Exogenous calprotectin appeared to induce dendritic extension in SH-SY5Y cell culture in a dose-dependent manner. Calprotectin was found to be localized to microglia. These findings suggest that increased levels of calprotecitn in the brain may reflect inflammatory processes, which play a role in the pathogenesis of major psychiatric disorders. Furthermore, calprotectin may influence dendritic plasticity.

Evidence for morphological alterations in prefrontal white matter glia in schizophrenia and bipolar disorder

“…Inflammation may therefore be present in a subset of patients with schizophre nia, consistent with findings in grey matter in individuals with this disorder. 48,49 Limitations When interpreting our results some methodological limita tions should be kept in mind. First, we identified oligoden drocytes using a nonspecific histological stain, an approach used in several previous studies of this cell population.…”

Interaction of clozapine and its nitrenium ion with rat D2 dopamine receptors: in vitro binding and computational study

“…Nevertheless, in pathophysiological conditions when the redox potential of the extracellular fluids can vary greatly, the interaction of the drug with the target can be modified consequently. This is not so hypothetical since severe disorders like schizophrenia are frequently associated with neurodegenerative processes and inflammatory events [44][45][46]. In another context, food deprivation is recently shown to affect brain oxidation status in rat especially with a significant increase in H 2 O 2 production [47].…”

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

“…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]. Additionally, there were significantly more QUIN-immunoreactive microglial cells in the CA1 hippocampal subregions of schizophrenia patients.…”

“…However, three other studies reported no differences between depressed patients and controls in IBA-1-and CD68- [24], HLA-DR- [33], and CD68- [42] positive microglial density.…”