Expression of miRNAs in the brain of dogs with visceral leishmaniasis

• Grant number: 22/08163-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2023
• End date: June 30, 2024
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Gisele Fabrino Machado
• Grantee: Giulia Gonçalves Jussiani
• Host Institution: Faculdade de Medicina Veterinária (FMVA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

Canine visceral leishmaniasis (CanVL) is a chronic, invariably progressive disease with high clinical variability, including neurological disorders. Due to the inflammatory changes in the brain, it is currently known that chronically infected dogs can present significant neurological deficits. Despite the clinical importance of this disorder, there are few reports that characterize neurological lesions in VL. Previous studies carried out in dogs with CVL showed the presence of brain inflammation by observing the infiltration of T lymphocytes, activation of glial cells, degenerative alterations of neurons, meningitis, choroiditis, in addition to the activation of metalloproteinases and alteration in the gene expression of chemokines and of pro-inflammatory cytokines. The role of miRNAs in the regulation of the expression of proteins fundamental for the function, differentiation and development of cell types of the immune system is known; and the deregulation of miRNAs activity seems to be involved in several diseases. In the nervous system, the balance between different phenotypic states of microglia and astrocytes can promote inflammation or tissue repair and influence the progression of inflammatory disorders. MiRNAs operate by activating or modulating glial cells, and can exacerbate or restrict the signaling of an inflammatory process. In addition, in CVL, because cellular immune suppression is crucial for its progression, it is known that miRNAs and their immune regulation are essential for changing the pattern of the response. Thus, in continuity with previous projects that used the dog as a model, the present study seeks to better understand the pathogenesis of the neurological alterations caused by CVL, through the evaluation of miRNA expression in the brain of dogs with visceral leishmaniasis.