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Temporal dynamics of the inflammatory response in amphibians

Grant number: 19/24950-4
Support type:Regular Research Grants
Duration: May 01, 2020 - April 30, 2022
Field of knowledge:Biological Sciences - Physiology - Compared Physiology
Principal Investigator:Fernando Ribeiro Gomes
Grantee:Fernando Ribeiro Gomes
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Sandra Marcia Muxel ; Stefanny Christie Monteiro Titon ; Vania Regina de Assis

Abstract

In recent decades, there has been a steep decline in amphibian populations around the globe. This decline is associated with multiple causes acting in a synergistic way, highlighting the increase in the prevalence and outbreaks of emerging diseases, the loss, fragmentation and disconnection of habitats, environmental pollution and climate change in multiple scales. In this context of exposure of amphibians to multiple stressors and pathogens, it is imperative a better understanding of the endogenous defense processes in this group and their modulation by stress response mediators. Considering these mediators, we highlight glucocorticoids and melatonin, hormones that play a prominent role in immunomodulatory activity. The objective of this project is to evaluate the temporal dynamics of changes in hormone secretion and gene expression of cytokines that participate in the assembly and regulation of the inflammatory response in anurans following an immune challenge. Our hypothesis is that, during three successive phases of the dynamics of the inflammatory process, we will first observe an increase in the production of pro-inflammatory cytokines, activation of the hypothalamic-pituitary-interrenal axis and inhibition of the central secretion of melatonin. The second phase should be characterized by an increase in the expression of regulatory cytokines. Finally, the third phase should be characterized by reduced hypothalamic-pituitary-interrenal axis activity, resumption of central melatonin secretion, and reduced expression of proinflammatory and regulatory cytokines. To test this hypothesis, immunological challenges will be performed with lipopolysaccharide (LPS), mimicking a bacterial infection in toads (Rhinella diptycha) and bullfrogs (Rana catesbeiana). We will follow the dynamics of hormone secretion (corticosterone and melatonin) in the circulation, expression of the enzymes of the melatonin production pathway in the brain and eyes, and the production of different cytokines in the spleen in response to this immunological challenge, by using RNAseq to analyzes transcriptome data and identify genes differentially expressed in response to LPS. (AU)