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Modulatory effects of the cholinergic system and nicotinic receptors on a murine model of acute lung injury induced by LPS

Grant number: 18/15738-9
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2018
Status:Discontinued
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Carla Máximo Prado
Grantee:Nathalia Montouro Pinheiro Menegasso
Home Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
Associated scholarship(s):19/15665-4 - Modulatory effects of the cholinergic system and nicotinic receptors on a murine model of acute lung injury induced by LPS, BE.EP.PD

Abstract

Acute lung injury (ALI) is characterized by sudden onset, polymorphonuclear cells recruitment and release of pro-inflammatory mediators, which can induce changes in cytokines. The reduction of vesicular transport of acetylcholine (VAChT) reduces the release of ACh, the main mediator of anti-inflammatory cholinergic system (AICS), modulating pulmonary inflammation. Aims: To evaluate the effect of the cholinergic system and nicotinic receptors on LPS-induced counter fluids, with emphasis on: - 1. Assess whether LPA is applied in LPS at the low dose induced changes in lungs in animals with VAChT reduction; - 2. Evaluate whether LPS-induced LPA modulates the expression of nicotinic receptors in animals. Aims 3 and 4 area conditional in favor of the Non-External Research Internship Grant (BEPE), which will be further requested. -3. Reaction is a function and expression of nicotinic receptors is subject to change in wild and mutant VAChT animals in excess or not at LPS instillation; 4. Evaluate the side effects on LPA produced by LPS in wild mice and mutant VAChT and also in C57BL animals. Methods: VAChT male mice (70% reduction in VAChT) wereintratracheal instillated with LPS and at 24 hours after, we will evaluatelung morphofunctional alterations (pulmonary components and cytokines) of the AICS in the lung (evaluation of nicotinic receptors and others). We will treat part of the animals with PNU, a nicotinic receptor agonist, to alert if the stimulus of this receptor reverts as the changes observed in the VAChT animals. The main part is required for goals 3 and 4 should not be external and conditional back. A data analysis is performed through the SigmaStat program.