Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment

• Grant number: 14/50427-3
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: July 01, 2014
• End date: January 31, 2015
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Cristoforo Scavone
• Grantee: Cristoforo Scavone
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

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. Here we report that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism involving NF-KB 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 interleukin (IL)-1a, IL-1{3 and TNF-a levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1{3, interferon (IFN)-y, RANTES, TNF-a 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 in an animal model of systemic bacterial infection. (AU)