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CENTRAL NERVOUS SYSTEM CHANGES IN A MODEL OF ACUTE PULMONARY INJURY INDUCED BY INTRATRACHEAL LPS: EVALUATION OF CHOLINERGIC COMPONENTS, IBA-1 AND BDNF

Grant number: 22/15777-0
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2023
Effective date (End): June 30, 2024
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Carla Máximo Prado
Grantee:Priscila Santos Barbosa
Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil

Abstract

Acute Respiratory Distress Syndrome (ARDS) is a severe lung disease that leads to respiratory failure, with several causes including bacterial and/or viral pneumonia. To fight the injury, the immune system is triggered to recruit defense cells, this inflammatory process, when exacerbated, damages the lung tissue and compromises its function of oxygenating the blood and removing carbon dioxide (CO2), as it directly affects the integrity of the alveolar barrier. -capillary, resulting in hypoxemia and hypercapnia. This inflammatory process can reach the central nervous system (CNS), resulting in neuroinflammation, where there is an exaggerated production of local inflammatory cytokines, compromising its structures with possible changes in cognition and behavior, as already described in the literature. Within this context, the anti-inflammatory cholinergic system can act by attenuating the inflammatory process and therefore components of this system could be altered in the face of the exacerbated inflammatory response. Objective: To assess whether there are alterations in the components of the cholinergic system in the lung and in the CNS in an APL model. Methodology: Lungs and CNS structures from male BALB/C mice that were divided into 3 groups will be used: the control, which received intratracheal instillation with saline; the experimental group that received intratracheal instillation of LPS and subdivided into 24h and 48h. The animals have already been euthanized and are part of a Master's project by our group. Histological sections of the lung and CNS will be performed. In the lung will be analyzed, by morphometric analysis, the index of collapse and distention and inflammation. The expression of ±7 nAChR associated with VAChT and macrophages will be evaluated by immunofluorescence, by double staining. In the CNS, the protein expression of Iba-1 and BDNF will be evaluated by immunohistochemistry. In all tissues (CNS and lung) the gene expression of VAChT, AChE, ±7 nAChR, ±4²2 nAChR will be evaluated. Statistical analysis: Statistical analysis will be performed by One-Way ANOVA using the Graph-Prisma Program and results with p<0.05 will be considered significant. Expected results: In the present project, it is expected that pulmonary inflammation (detected by increased inflammatory cells and an increase in the collapse and expansion index) will be associated with increased expression of ±7 nAChR and BDNF in the lung, in an attempt to control the inflammatory response induced by LPS and increased stimulation of the nervous system, respectively. In other studies, attempts have been made to increase cholinergic response in inflammatory situations, resulting in an increase in ²-2 and VAChT expression in the lung and a reduction in acetylcholinesterase. In the CNS, it is expected that neuroinflammation will lead to a reduction in BDNF, as this factor is involved in CNS protection, and an increase in Iba-1, a microglia marker, the main inflammatory cell of the CNS, which would justify the presence of observed behavioral changes.

News published in Agência FAPESP Newsletter about the scholarship:
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