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Neuroinflammation in the dorsolateral prefrontal cortex in elderly chronic schizophrenia

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Cognitive deterioration and symptom progression occur in schizophrenia over the course of the disorder. A dysfunction of the immune system/neuroinflammatory pathways has been linked to schizophrenia (SZ). These altered processes in the dorsolateral prefrontal cortex (DLPFC) could contribute to the worsening of the deficits. However, limited studies are available in this brain region in elderly population with long-term treatments. In this study, we explore the possible deregulation of 21 key genes involved in immune homeostasis, including pro- and anti- inflammatory cytokines, cytokine modulators (toll-like receptors, colony-stimulating factors, and members of the complement system) and microglial and astroglial markers in the DLPFC in elderly chronic schizophrenia. We used quantitative real-time reverse transcriptase poly- merase chain reaction (RT-PCR) on extracts from postmortem DLPFC of elderly subjects with chronic SZ ( n = 14) compared to healthy control individuals ( n = 14). We report that CSF1R, TLR4, IL6, TNF α, TNFRSF1A, IL10, IL10RA, IL10RB, and CD68 were down-regulated in elderly SZ subjects. Moreover, we found that the expression levels of all the altered inflammatory genes in SZ correlated with the microglial marker CD68 . However, no associations were found with the astroglial marker GFAP . This study reveals a decrease in the gene expression of cytokines and immune response/inflammation mediators in the DLPFC of elderly subjects with chronic schizophrenia, supporting the idea of a dysfunction of these processes in aged patients and its possible relationship with active microglia abundance. These findings include elements that might contribute to the cognitive decline and symptom progression linked to DLPFC functioning at advanced stages of the disease.

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European Neuropsychopharmacology, 2019, vol. 29, num. 3, p. 384-396

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Articles publicats en revistes (Patologia i Terapèutica Experimental)

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Neuroinflammation in the dorsolateral prefrontal cortex in elderly chronic schizophrenia