Article
Memory impairment in chronic experimental Chagas disease: Benznidazole therapy reversed cognitive deficit in association with reduction of parasite load and oxidative stress in the nervous tissue
Registro en:
PEREIRA, Glaucia Vilar et al. Memory impairment in chronic experimental Chagas disease: Benznidazole therapy reversed cognitive deficit in association with reduction of parasite load and oxidative stress in the nervous tissue. Plos One, v. 16, n.1, e0244710, 21p, Jan. 2021.
1932-6203
10.1371/journal.pone.0244710
Autor
Pereira, Glaucia Vilar
Barrios, Leda Castaño
Silva, Andrea Alice da
Batista, Angelica Martins
Pereira, Isabela Resende
Moreira, Otacílio Cruz
Britto, Constança
Santos, Hilton Antônio Mata dos
Vieira, Joseli Lannes
Resumen
Memory impairment has been associated with chronic Chagas disease (CD), a neglected
tropical disease caused by the protozoan parasite Trypanosoma cruzi. In degenerative diseases,
memory loss has been associated with increased oxidative stress, revealed as
enhanced lipid peroxidation, in the cerebral cortex. Benznidazole (Bz), a trypanocidal drug
efficient to reduce blood parasite load in the acute and chronic phases of infection, showed
controversial effects on heart disease progression, the main clinical manifestation of CD.
Here, we evaluated whether C57BL/6 mice infected with the Colombian type I T. cruzi strain
present memory deficit assessed by (i) the novel object recognition task, (ii) the open field
test and (iii) the aversive shock evoked test, at 120 days post infection (dpi). Next, we tested
the effects of Bz therapy (25mg/Kg/day, for 30 consecutive days) on memory evocation,
and tried to establish a relation between memory loss, parasite load and oxidative stress in
the central nervous system (CNS). At 120 dpi, T. cruzi-infected mice showed memory
impairment, compared with age-matched non-infected controls. Bz therapy (from 120 to
150 dpi) hampered the progression of habituation and aversive memory loss and, moreover,
reversed memory impairment in object recognition. In vehicle-administered infected mice,
neuroinflammation was absent albeit rare perivascular mononuclear cells were found in
meninges and choroid plexus. Bz therapy abrogated the infiltration of the CNS by inflammatory
cells, and reduced parasite load in hippocampus and cerebral cortex. At 120 and 150
dpi, lipid peroxidation was increased in the hippocampus and cortex tissue extracts. Notably,
Bz therapy reduced levels of lipid peroxidation in the cerebral cortex. Therefore, in xperimental chronic T. cruzi infection Bz therapy improved memory loss, in association
with reduction of parasite load and oxidative stress in the CNS, providing a new perspective
to improve the quality of life of Chagas disease patients.