Changes in NF-kB in glia and neuron induced by intermittent fasting in TLR4 KO mice

• Grant number: 14/03613-6
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: May 01, 2014
• End date: October 31, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Cristoforo Scavone
• Grantee: Andrea Rodrigues Vasconcelos
• Supervisor: Mark P. Mattson
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: National Institutes of Health, Baltimore (NIH), United States
• Associated to the scholarship: 11/12255-8 - Influence of TLR4 receptors in behavioral and neurochemical alterations caused by intermittent fasting in C3H/HeJ mice, BP.DR

Abstract

The dietary energy restriction (DER) exposes the organisms to a moderate nutritional stress that not only stimulates the stress proteins, but also the defense mechanisms of the body, making it more resistant to toxic or potentially deleterious stimuli. In general, the DER seems to act in pathways associated with inflammatory response and cell survival, and increase the cell resistance against oxidative stress, thereby involving the modulation of transcription factors such as NF-ºB. However, little is known about the molecular mechanisms involved and the role of Toll-like receptor (TLR) 4 in modulating the beneficial effects of DER. However, our preliminary results have shown that intermittent fasting causes a significant reduction in TLR4 messenger RNA levels in rat hippocampus, suggesting an involvement of this receptor in the effects of DER. This project aims to evaluate the influence of TLR4 in the neuroprotective effects induced by intermittent fasting on the signaling mechanisms associated with the transcription factor NF-ºB in neurons and glia. A better understanding of these physiological processes may allow the development of new strategies for pharmacological interventions aimed at promoting longevity and healthy aging, as well as for the treatment of neurodegenerative disorders. (AU)