Analysis of the activation of NF-kB in the CNS of rats submitted to chronic unpredictable stress as hormesis model in the presence of an inflammatory stimulus

• Grant number: 13/15865-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date until: October 01, 2013
• End date until: July 31, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Cristoforo Scavone
• Grantee: Karen Mathidios de Paiva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

There are evidences that stress is a contributing factor in human disease, and in particular cardiovascular disease, as well as depression, neurodegenerative disorders and HIV/AIDS. Data from our laboratory have shown that chronic unpredictable stress (CUS) enhances the activation of the transcription factor NF-ºB and expression of pro-inflammatory genes induced by lipopolysaccharide (LPS) administration. NF-ºB is a transcription factor linked to the immune system that is involved in protection, proliferation and cellular plasticity in CNS. Changes in the activation of this transcription factor can play an important role in diseases related to aging and stress. Hormesis is defined as an adaptive response of cells and organisms to a moderate stress (usually intermittent). Examples include exercise, intermittent fasting (IF) and exposure to low doses of certain herbal medicines, such as curcumine and resveratrol. Studies have shown that hormesis can increase resistance of neurons to excitotoxic stress and may ameliorate age-related deficits in cognitive function through mechanisms involving activation of adaptive cellular stress response pathways. The aim of the present project is to evaluate whether intermittent CUS schedule (48h interval between each stress stimulus) can decrease LPS induced inflammatory signaling cascade in the CNS. These studies should contribute to a better understanding of the molecular mechanisms related to stress-response hormesis, generating possible new drug targets to neurodegenerative diseases.