Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment

Author(s)

Vasconcelos, Andrea R. ^[1] ; Yshii, Lidia M. ^[1] ; Viel, Tania A. ^[2] ; Buck, Hudson S. ^[3] ; Mattson, Mark P. ^[4] ; Scavone, Cristoforo ^[1] ; Kawamoto, Elisa M. ^{[1, 4]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Arts Sci & Humanities, BR-03828080 Sao Paulo - Brazil

^[3] Santa Casa Sao Paulo Med Sch, Dept Physiol Sci, BR-01221020 Sao Paulo - Brazil

^[4] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 - USA

• Document type: Journal article
• Source: JOURNAL OF NEUROINFLAMMATION; v. 11, MAY 6 2014.
• Web of Science Citations: 59

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-B 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-1 alpha, IL-1 beta and TNF-alpha levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1 beta, IFN-gamma, RANTES, TNF-alpha 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. (AU)

• FAPESP's process: 06/57729-9 - Amyloid-beta (Abeta) peptide activates NF-kB through NMDA-Ras pathway in cerebellar primary cell culture
• Grantee: Elisa Mitiko Kawamoto Iwashe
• Support Opportunities: Research Grants - Meeting - Abroad
• FAPESP's process: 09/11915-4 - Behavioural and biochemical changes induced by calorie restriction in LPS signalling in central nervous system
• Grantee: Andrea Rodrigues Vasconcelos
• Support Opportunities: Scholarships in Brazil - Master