Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Vilar-Pereira, Glaucia, Castaño Barrios, Leda, da Silva, Andrea Alice, Martins Batista, Angelica, Resende Pereira, Isabela, Cruz Moreira, Otacílio, Britto, Constança, Mata dos Santos, Hílton Antônio, Lannes-Vieira, Joseli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785227/
https://www.ncbi.nlm.nih.gov/pubmed/33400707
http://dx.doi.org/10.1371/journal.pone.0244710
_version_ 1783632398578089984
author Vilar-Pereira, Glaucia
Castaño Barrios, Leda
da Silva, Andrea Alice
Martins Batista, Angelica
Resende Pereira, Isabela
Cruz Moreira, Otacílio
Britto, Constança
Mata dos Santos, Hílton Antônio
Lannes-Vieira, Joseli
author_facet Vilar-Pereira, Glaucia
Castaño Barrios, Leda
da Silva, Andrea Alice
Martins Batista, Angelica
Resende Pereira, Isabela
Cruz Moreira, Otacílio
Britto, Constança
Mata dos Santos, Hílton Antônio
Lannes-Vieira, Joseli
author_sort Vilar-Pereira, Glaucia
collection PubMed
description 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 experimental 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.
format Online
Article
Text
id pubmed-7785227
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-77852272021-01-13 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 Vilar-Pereira, Glaucia Castaño Barrios, Leda da Silva, Andrea Alice Martins Batista, Angelica Resende Pereira, Isabela Cruz Moreira, Otacílio Britto, Constança Mata dos Santos, Hílton Antônio Lannes-Vieira, Joseli PLoS One Research Article 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 experimental 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. Public Library of Science 2021-01-05 /pmc/articles/PMC7785227/ /pubmed/33400707 http://dx.doi.org/10.1371/journal.pone.0244710 Text en © 2021 Vilar-Pereira et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Vilar-Pereira, Glaucia
Castaño Barrios, Leda
da Silva, Andrea Alice
Martins Batista, Angelica
Resende Pereira, Isabela
Cruz Moreira, Otacílio
Britto, Constança
Mata dos Santos, Hílton Antônio
Lannes-Vieira, Joseli
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785227/
https://www.ncbi.nlm.nih.gov/pubmed/33400707
http://dx.doi.org/10.1371/journal.pone.0244710
work_keys_str_mv AT vilarpereiraglaucia memoryimpairmentinchronicexperimentalchagasdiseasebenznidazoletherapyreversedcognitivedeficitinassociationwithreductionofparasiteloadandoxidativestressinthenervoustissue
AT castanobarriosleda memoryimpairmentinchronicexperimentalchagasdiseasebenznidazoletherapyreversedcognitivedeficitinassociationwithreductionofparasiteloadandoxidativestressinthenervoustissue
AT dasilvaandreaalice memoryimpairmentinchronicexperimentalchagasdiseasebenznidazoletherapyreversedcognitivedeficitinassociationwithreductionofparasiteloadandoxidativestressinthenervoustissue
AT martinsbatistaangelica memoryimpairmentinchronicexperimentalchagasdiseasebenznidazoletherapyreversedcognitivedeficitinassociationwithreductionofparasiteloadandoxidativestressinthenervoustissue
AT resendepereiraisabela memoryimpairmentinchronicexperimentalchagasdiseasebenznidazoletherapyreversedcognitivedeficitinassociationwithreductionofparasiteloadandoxidativestressinthenervoustissue
AT cruzmoreiraotacilio memoryimpairmentinchronicexperimentalchagasdiseasebenznidazoletherapyreversedcognitivedeficitinassociationwithreductionofparasiteloadandoxidativestressinthenervoustissue
AT brittoconstanca memoryimpairmentinchronicexperimentalchagasdiseasebenznidazoletherapyreversedcognitivedeficitinassociationwithreductionofparasiteloadandoxidativestressinthenervoustissue
AT matadossantoshiltonantonio memoryimpairmentinchronicexperimentalchagasdiseasebenznidazoletherapyreversedcognitivedeficitinassociationwithreductionofparasiteloadandoxidativestressinthenervoustissue
AT lannesvieirajoseli memoryimpairmentinchronicexperimentalchagasdiseasebenznidazoletherapyreversedcognitivedeficitinassociationwithreductionofparasiteloadandoxidativestressinthenervoustissue