title: Impairment of autophagy in the central nervous system during lipopolysaccharide-induced inflammatory stress in mice.
abstract: BACKGROUND
  Current evidence suggests a central role for autophagy in many neurodegenerative diseases including Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis. Furthermore, it is well admitted that inflammation contributes to the progression of these diseases. Interestingly, crosstalks between autophagy and inflammation have been reported in vitro and at the peripheral level such as in Crohn's disease. However, the impact of systemic inflammation on autophagic components in the brain remains to be documented. Therefore, this study monitored autophagy markers after acute and chronic lipopolysaccharide (LPS)-induced inflammatory stress in mice.
  
  
  RESULTS
  We showed that acute inflammation, 24 h post-intraperitoneal 10 mg/kg LPS, substantially increased cytokine production (Interleukin(IL)-1β, Tumor necrosis factor (TNF)-α and IL-6), decreased the levels of autophagy markers (Beclin-1, p62 and LC3 II) and reduced p70S6K activation in cortex and hippocampus. In hippocampus, IL-1β levels and LC3 II expression were positively and highly correlated and a negative correlation was noted between TNF-α levels and p70S6K activation. Chronic inflammation by injection of 0.5 mg/kg LPS every three days during three months led to a moderate IL-1β production and decreased TNF-α levels. Interestingly, Beclin-1 and LC3 II levels decreased while those of p62 increased. Cortical IL-1β levels positively correlated with Beclin-1 and LC3 II and on the contrary inversely correlated with p62.
  
  
  CONCLUSIONS
  The present study is the first showing links between IL-1β-mediated inflammation and autophagy in the brain. It could open to new therapeutic strategies in brain diseases where regulation impairment of inflammation and autophagy progress with the severity of diseases.
authors.affiliation: EA3808 molecular Targets and Therapeutic of Alzheimer's disease, University of Poitiers, Poitiers F-86073, France. arnaudfrancois85@gmail.com.
authors.forename: Arnaud
authors.initials: A
authors.lastname: François
authors.forename: Faraj
authors.initials: F
authors.lastname: Terro
authors.forename: Nathalie
authors.initials: N
authors.lastname: Quellard
authors.forename: Béatrice
authors.initials: B
authors.lastname: Fernandez
authors.forename: Damien
authors.initials: D
authors.lastname: Chassaing
authors.forename: Thierry
authors.initials: T
authors.lastname: Janet
authors.forename: Agnès
authors.initials: A
authors.lastname: Rioux Bilan
authors.forename: Marc
authors.initials: M
authors.lastname: Paccalin
authors.forename: Guylène
authors.initials: G
authors.lastname: Page
mesh_terms: D000818:Animals; D001343:Autophagy; D015415:Biomarkers / Q000378:metabolism; D002490:Central Nervous System / Q000473:pathology*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D015398:Signal Transduction; D013312:Stress, Physiological; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D058570:TOR Serine-Threonine Kinases