Neuroinflammation in the dorsolateral prefrontal cortex in elderly chronic schizophrenia
Por:
López-González I, Pinacho R, Vila E, ANA ESCANILLA CASAL, Ferrer I and Ramos B
Publicada:
1 mar 2019
Ahead of Print:
7 ene 2019
Resumen:
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 polymerase 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 alpha, 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. (c) 2018 Elsevier B.V. and ECNP. All rights reserved.
Filiaciones:
López-González I:
Neuropathology, Bellvitge University Hospital, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
Pinacho R:
Psiquiatria Molecular, Institut de Recerca Sant Joan de Déu, Santa Rosa 39-57, 08950 Esplugues de Llobregat, Spain
Vila E:
Psiquiatria Molecular, Institut de Recerca Sant Joan de Déu, Santa Rosa 39-57, 08950 Esplugues de Llobregat, Spain
Parc Sanitari Sant Joan de Déu, Dr. Antoni Pujadas, 42, 08830 Sant Boi de Llobregat, Spain
ANA ESCANILLA CASAL:
Parc Sanitari Sant Joan de Déu, Dr. Antoni Pujadas, 42, 08830 Sant Boi de Llobregat, Spain
Banc de Teixits Neurologics, Parc Sanitari Sant Joan de Déu, 08830 Sant Boi de Llobregat, Spain
Ferrer I:
Neuropathology, Bellvitge University Hospital, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
Departament de Patologia i Terapeutica Experimental, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
CIBERNED (Biomedical Network Research Center of Neurodegenerative Diseases), Ministry of Economy, Industry and Competitiveness Institute of Health Carlos III, Madrid, Spain
Ramos B:
Psiquiatria Molecular, Institut de Recerca Sant Joan de Déu, Santa Rosa 39-57, 08950 Esplugues de Llobregat, Spain
Parc Sanitari Sant Joan de Déu, Dr. Antoni Pujadas, 42, 08830 Sant Boi de Llobregat, Spain
Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM (Biomedical Network Research Center of Mental Health), Ministry of Economy, Industry and Competitiveness Institute of Health Carlos III, Madrid, Spain
Dept. de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain
Green Accepted
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