title: Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment.
abstract: BACKGROUND
  Systemic bacterial infections often result in enduring cognitive impairment and are a risk factor for dementia. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that intermittent fasting (IF) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of IF on the cognitive sequelae of systemic and brain inflammation is unknown.
  
  
  METHODS
  Rats on IF for 30 days received 1 mg/kg of lipopolysaccharide (LPS) or saline intravenously. Half of the rats were subjected to behavioral tests and the other half were euthanized two hours after LPS administration and the hippocampus was dissected and frozen for analyses.
  
  
  RESULTS
  Here, we report that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism involving NF-κB activation, suppression of the expression of pro-inflammatory cytokines, and enhancement of neurotrophic support. Treatment of rats with LPS resulted in deficits in cognitive performance in the Barnes maze and inhibitory avoidance tests, without changing locomotor activity, that were ameliorated in rats that had been maintained on the IF diet. IF also resulted in reduced levels of mRNAs encoding the LPS receptor TLR4 and inducible nitric oxide synthase (iNOS) in the hippocampus. Moreover, IF prevented LPS-induced elevation of IL-1α, IL-1β and TNF-α levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1β, IFN-γ, RANTES, TNF-α and IL-6 levels.
  
  
  CONCLUSIONS
  Taken together, our results suggest that IF induces adaptive responses in the brain and periphery that can suppress inflammation and preserve cognitive function in an animal model of systemic bacterial infection.
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Vasconcelos
authors.forename: Lidia M
authors.initials: LM
authors.lastname: Yshii
authors.forename: Tania A
authors.initials: TA
authors.lastname: Viel
authors.forename: Hudson S
authors.initials: HS
authors.lastname: Buck
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.affiliation: Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo 05508-900, Brazil. criscavone@usp.br.
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Scavone
authors.forename: Elisa M
authors.initials: EM
authors.lastname: Kawamoto
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D005215:Fasting; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced* / Q000628:therapy*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D052247:Nitric Oxide Synthase Type II