Journal Article

Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment

Mattson, Mark P, Vasconcelos, Andrea R, Scavone, Cristoforo, Kawamoto, Elisa M, Yshii, Lidia M, Viel, Tania A, Buck, Hudson S

2014

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V
• Subject: Aging / Analysis / Animal cognition / Animals / Avoidance Learning - drug effects / Avoidance Learning - physiology / Bacterial infections / Biomedical and Life Sciences / Biomedicine / Brain - drug effects / Brain - metabolism / Brain - pathology / Brain research / Brain-derived neurotrophic factor / Care and treatment / Cognitive ability / Complications and side effects / Cytokines / Cytokines - genetics / Cytokines - metabolism / Design of experiments / Development and progression / Diet / Disease Models, Animal / Electrophoretic Mobility Shift Assay / Fasting / Gene Expression Regulation - drug effects / Genetic aspects / Health aspects / Immune system / Immunology / Inflammation / Inflammation - chemically induced / Inflammation - therapy / Lipopolysaccharides - toxicity / Male / Maze Learning - drug effects / Memory / Memory Disorders - chemically induced / Memory Disorders - pathology / Memory Disorders - therapy / Motor Activity - drug effects / Motor Activity - physiology / Neurobiology / Neurology / Neurons / Neurophysiology / Neurosciences / NF-kappa B - metabolism / Nitric Oxide Synthase Type II - genetics / Nitric Oxide Synthase Type II - metabolism / Patient outcomes / Psychomotor Performance - drug effects / Psychomotor Performance - physiology / Rats / Rats, Wistar / Risk factors / Rodents / Stroke / Studies / TNF inhibitors / Toll-Like Receptor 4 - genetics / Toll-Like Receptor 4 - metabolism