Functional characterization of astrocytes in the brain of dogs with visceral leishmaniasis: Detection of Aquaporin-1 (AQP-1) in perivascular and periventricular astrocytes

• Grant number: 23/06671-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2023
• End date: July 31, 2024
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Gisele Fabrino Machado
• Grantee: Maria Eduarda Escobar Marchioni
• 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. Continuing 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 microglia polarization (M1/M2) and the functional profile of astrocytes in dog brains naturally infected, using immunohistochemistry. Among the proteins expressed by astrocytes, we intend to study aquaporin 4, which, among other functions, has the capacity to act as a neuroimmunological inducer, participating in the communication between astrocytes and microglia, in addition to maintaining the selective function of the blood-brain barrier. Another protein to be studied that has been associated with astrocytic activation is survivin.