miRNAs and gene expression of cytokines in the brain of dogs with visceral leishmaniasis

• Grant number: 23/09159-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2023
• End date: September 30, 2024
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Gisele Fabrino Machado
• Grantee: Marco Antonio Issa Zoccoler
• Host Institution: Faculdade de Medicina Veterinária (FMVA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

Canine visceral leishmaniasis (CVL) is a chronic, invariably progressive disease with high clinical variability, including neurological disorders. Despite the clinical importance of the disease for humans and dogs, reports characterizing neurological lesions in VL and explaining its pathogenesis are still scarce. Previous studies carried out in dogs with VL showed the presence of encephalic inflammation, including meningitis and choroiditis, activation of glial cells, in addition to activation of metalloproteinases, alteration in the gene expression of chemokines and pro-inflammatory cytokines. The balance between different phenotypic states of microglia and astrocytes can promote inflammation or tissue repair and influence the progression of inflammatory disorders of nervous tissue. miRNAs operate by activating or modulating glial cells, and can promote or restrict inflammatory signaling, exacerbating or stimulating the consequences of an inflammatory process in nervous tissue. 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 related to the activation and modulation of microglia (M1/M2) and the functional profile of astrocytes in brains of naturally infected dogs. Among the objectives of the IC student is the evaluation of the expression of the genes for Toll-2, Toll-4 and Toll-8 receptors and the genes of the cytokines TNF-±, INF-³, IL-6 and IL-10 in the nervous tissue of dogs with visceral leishmaniasis and dogs with leishmaniasis and positive serology for other infectious agents.