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Evaluation of the neuroimmune mechanisms in the stress-induced decrease of neutrophil activity and migration in a murine model of intestinal inflammation

Grant number: 12/21767-5
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): April 01, 2013
Effective date (End): March 31, 2014
Field of knowledge:Agronomical Sciences - Veterinary Medicine - Animal Pathology
Principal researcher:Sandra Helena Poliselli Farsky
Grantee:Viviane Ferraz de Paula
Supervisor abroad: Elena Gonzalez-Rey
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Instituto de Parasitología y Biomedicina “López-Neyra” (IPBLN), Spain  

Abstract

Crohn’s disease and ulcerative colitis are inflammatory diseases of the gastrointestinal tract which are associated to an increased risk of colon cancer. These conditions affect millions of people all over the world and are responsible for a considerable public spending in developed and developing countries, such as Brazil. The inflammatory bowel diseases, known as IBD, are chronic inflammatory conditions which lead to prolonged and, sometimes, to an irreversible injury of the structure and function of the gastrointestinal system. IBD's etiology is not completely understood, however several studies show that multiple factors, including genetic and environmental factors, and also immunological factors against the commensal bacterial flora. It is known that the environmental factors, such as physical and/or psychological stress, have a positive correlation with the onset and relapse of these disease and the investigation of these parameters is the main goal of our ongoing postdoctoral project. The results obtained during the first year of fellowship show that the restraint stress was able to worsen the DSS-induced colitis, as observed by the clinical signs of the disease, and also decreased both the activation and migration of neutrophils to the site of inflammation, i.e., the colon. These results are going to be included in a manuscript to be sent for publication soon. Nevertheless, we believe that it is essential to understand the neuroimmune mechanisms, which are triggered by the stress response, in the decrease of neutrophil migration to the colon of the animals submitted to the colitis. Therefore, this application for a fellowship abroad, specifically in the Instituto de Parasitologia e Biomedicina - López-Neyra in Granada, Spain, coordinated by Dr. Elena Gonzalez Rey, is extremely important since they are internationally recognized as an outstanding group in the field of psychoneuroimmunology of inflammatory diseases and also they have an excellent laboratory structure. Morevoer, Dra Elena has in the department animal facility mice that are knockout for the neuropeptide corstistatin, which has been shown to be a modulator of the central nervous system and immune system activity; there are also some evidences showing that cortistatin may modulate IBD development. Thus, the evaluation of the role of cortistatin, associated with the role of the HPA axis (which was initially proposed in this project), will shed some light in the neuroimmune mechanisms involved in the worsening of the colitis during the stress response. (AU)

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