RT Journal Article
T1 Differential regulation of the TLR4 signalling pathway in post-mortem prefrontal cortex and cerebellum in chronic schizophrenia: Relationship with SP transcription factors
A1 Mac-Dowell Mata, Karina Soledad
A1 Pinacho, Raquel
A1 Costa, Joan
A1 Ramos, Belén
A1 Leza Cerro, Juan Carlos
A1 García Bueno, Borja
AB Alterations in innate immunity may underlie the pathophysiology of schizophrenia (SZ). Toll-like receptor-4 (TLR4) is a master element of innate immunity. The specificity proteins (SPs), transcription factors recently implicated in SZ, are putative regulatory agents of this. This work was aimed at describing alterations in the TLR4 signalling pathway in postmortem brain prefrontal cortex (PFC) and cerebellum (CB) of 16 chronic SZ patients and 14 controls. The possible association of TLR4 pathway with SP1 and SP4 and SZ negative symptomatology is explored. In PFC, TLR4/myeloid differentiation factor 88 (MyD88)/inhibitory subunit of nuclear factor kappa B alpha (IκBα) protein levels were lower in SZ patients, while nuclear transcription factor-κB (NFκB) activity, cyclooxygenase-2 (COX-2) expression and the lipid peroxidation index malondialdehyde (MDA) appeared increased. The pattern of changes in CB is opposite, except for COX-2 expression that remained augmented and MDA levels unaltered. Network interaction analysis showed that TLR4/MyD88/IκBα/NFκB/COX-2 pathway was coupled in PFC and uncoupled in CB. SP4 co-expressed with TLR4 and NFκB in PFC and both SP1 and SP4 co-expressed with NFκB in CB. In PFC, correlation analysis found an inverse relationship between NFκB and negative symptoms. In summary, we found brain region-specific alterations in the TLR4 signalling pathway in chronic SZ, in which SP transcription factors could participate at different levels. Further studies are required to elucidate the regulatory mechanisms of innate immunity in SZ and its relationship with symptoms.
PB Elsevier
SN 0278-5846
YR 2017
FD 2017-10
LK https://hdl.handle.net/20.500.14352/96725
UL https://hdl.handle.net/20.500.14352/96725
LA eng
NO MacDowell KS, Pinacho R, Leza JC, Costa J, Ramos B, García-Bueno B. Differential regulation of the TLR4 signalling pathway in post-mortem prefrontal cortex and cerebellum in chronic schizophrenia: Relationship with SP transcription factors. Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):481-492. doi: 10.1016/j.pnpbp.2017.08.005. PMID: 28803924.
NO Centro de Investigación Biomédica en Red de Salud Mental
NO Ministerio de Economía, Comercio y Empresa (España)/Fondo Europeo de Desarrollo Regional
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 27 sept 2024