title: Rcor2 underexpression in senescent mice: a target for inflammaging?
abstract: BACKGROUND
  Aging is characterized by a low-grade systemic inflammation that contributes to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, little knowledge is currently available on the molecular processes leading to chronic neuroinflammation. In this context, recent studies have described the role of chromatin regulators in inflammation and longevity including the REST corepressor (Rcor)-2 factor, which seems to be involved in an inflammatory suppressive program.
  
  
  METHODS
  To assess the impact of Rcor2 in age-related inflammation, gene expression levels were quantified in different tissues and ages of the spontaneous senescence-accelerated P8 mouse (P8) using the SAMR1 mouse (R1) as a control. Specific siRNA transfection in P8 and R1 astrocyte cultures was used to determine Rcor2 involvement in the modulation of neuroinflammation. The effect of lipopolysaccharide (LPS) treatment on Rcor2 levels and neuroinflammation was analyzed both in vivo and in vitro.
  
  
  RESULTS
  P8 mice presented a dramatic decrease in Rcor2 gene expression compared with R1 controls in splenocytes, an alteration also observed in the brain cortex, hippocampus and primary astrocytes of these mice. Rcor2 reduction in astrocytes was accompanied by an increased basal expression of the interleukin (Il)-6 gene. Strikingly, intraperitoneal LPS injection in R1 mice downregulated Rcor2 in the hippocampus, with a concomitant upregulation of tumor necrosis factor (Tnf-α), Il1-β and Il6 genes. A negative correlation between Rcor2 and Il6 gene expression was also verified in LPS-treated C6 glioma cells. Knock down of Rcor2 by siRNA transfection (siRcor2) in R1 astrocytes upregulated Il6 gene expression while siRcor2 further increased Il6 expression in P8 astrocytes. Moreover, LPS activation provoked a further downregulation of Rcor2 and an amplified induction of Il6 in siRcor2-tranfected astrocytes.
  
  
  CONCLUSIONS
  Data presented here show interplay between Rcor2 downregulation and increased inflammation and suggest that Rcor2 may be a key regulator of inflammaging.
authors: María J
authors: MJ
authors: Alvarez-López
authors: Patricia
authors: P
authors: Molina-Martínez
authors: Marco
authors: M
authors: Castro-Freire
authors: Marta
authors: M
authors: Cosín-Tomás
authors: Rosa
authors: R
authors: Cristòfol
authors: Marcelina
authors: M
authors: Párrizas
authors: Rosa María
authors: RM
authors: Escorihuela
authors: Merce
authors: M
authors: Pallàs
authors: Coral
authors: C
authors: Sanfeliu
authors: Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Rosellón 149, E-08036 Barcelona, Spain. pkaliman@ub.edu.
authors: Perla
authors: P
authors: Kaliman
mesh_terms: D000375:Aging / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects; D056970:Co-Repressor Proteins; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D004660:Encephalitis / Q000139:chemically induced / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008745:Methylation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D056970:Co-Repressor Proteins; D016207:Cytokines; D004791:Enzyme Inhibitors; D006657:Histones; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D029362:Organic Anion Transporters, Sodium-Independent; C485650:Rcor2 protein, mouse; D012097:Repressor Proteins; C114338:organic anion transport protein 3