Article
Behavioral alterations in long-term Toxoplasma gondii infection of C57BL/6 mice are associated with neuroinflammation and disruption of the blood brain barrier
Registro en:
BARRIOS, Leda Castãno et al. Behavioral alterations in long-term Toxoplasma gondii infection of C57BL/6 mice are associated with neuroinflammation and disruption of the blood brain barrier. Plos One, v. 16, n. 10, 0258199, p. 1-30, Oct. 2021.
1932-6203
10.1371/journal.pone.0258199
Autor
Barrios, Leda Castãno
Pinheiro, Ana Paula da Silva
Gibaldi, Daniel
Silva, Andrea Alice
Silva, Patrícia Machado Rodrigues e
Roffê, Ester
Santiago, Helton da Costa
Gazzinelli, Ricardo Tostes
Mineo, José Roberto
Silva, Neide Maria
Vieira, Joseli Lannes
Resumen
The Apicomplexa protozoan Toxoplasma gondii is a mandatory intracellular parasite and
the causative agent of toxoplasmosis. This illness is of medical importance due to its high
prevalence worldwide and may cause neurological alterations in immunocompromised persons.
In chronically infected immunocompetent individuals, this parasite forms tissue cysts
mainly in the brain. In addition, T. gondii infection has been related to mental illnesses such
as schizophrenia, bipolar disorder, depression, obsessive-compulsive disorder, as well as
mood, personality, and other behavioral changes. In the present study, we evaluated the
kinetics of behavioral alterations in a model of chronic infection, assessing anxiety, depression
and exploratory behavior, and their relationship with neuroinflammation and parasite
cysts in brain tissue areas, blood-brain-barrier (BBB) integrity, and cytokine status in the
brain and serum. Adult female C57BL/6 mice were infected by gavage with 5 cysts of the
ME-49 type II T. gondii strain, and analyzed as independent groups at 30, 60 and 90 days
postinfection (dpi). Anxiety, depressive-like behavior, and hyperactivity were detected in the
early (30 dpi) and long-term (60 and 90 dpi) chronic T. gondii infection, in a direct association
with the presence of parasite cysts and neuroinflammation, independently of the brain tissue
areas, and linked to BBB disruption. These behavioral alterations paralleled the upregulation
of expression of tumor necrosis factor (TNF) and CC-chemokines (CCL2/MCP-1, CCL3/
MIP-1α, CCL4/MIP-1β and CCL5/RANTES) in the brain tissue. In addition, increased levels
of interferon-gamma (IFNγ), TNF and CCL2/MCP-1 were detected in the peripheral blood,
at 30 and 60 dpi. Our data suggest that the persistence of parasite cysts induces sustained
neuroinflammation, and BBB disruption, thus allowing leakage of cytokines of circulating plasma into the brain tissue. Therefore, all these factors may contribute to behavioral
changes (anxiety, depressive-like behavior, and hyperactivity) in chronic T. gondii infection.