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Influence of TLR2 and TLR4 receptors in behavioral and neurochemical alterations caused by intermitent fasting in knockout mice

Grant number: 12/25361-3
Support type:Regular Research Grants
Duration: April 01, 2013 - March 31, 2015
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Cristoforo Scavone
Grantee:Cristoforo Scavone
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Elisa Mitiko Kawamoto Iwashe

Abstract

Studies have shown that dietary energy restriction (DER) without malnutrition can increase resistance of neurons to excitotoxic stress and may ameliorate age-related deficits in cognitive function through hormetic mechanisms involving activation of adaptive cellular stress response pathways. Fundamental to the hormetic adaptive response is gene expression regulation. Although different stressors elicit unique signature responses, the comparison of prototypical hormetic inducers has highlighted the role played by a few transcription factors such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ºB), Forkhead box O (FOXO) and NFE2 related factor 2 (Nrf2). NF-ºB plays a key role in regulating the immune response to infection and has also been implicated in processes of synaptic plasticity and memory. FOXO and Nrf2 can enhance transcription of genes containing an antioxidant response element (ARE). Our data demonstrated that intermittent fasting can ameliorate cognitive deficits associated to LPS treatment, and suggest roles for TLR4 in this beneficial effect of DER. The aim of the present work is to investigate the influence of TLR4 and TLR2 receptors in the behavioral and neurochemical alterations caused by intermittent fasting in TLR4 and TLR2 knockout mice. (AU)