Participation of Central Muscarinic Receptors on the Nervous Form of Chagas Disease in Mice Infected via Intracerebroventricular with Colombian <i>Trypanosoma cruzi</i> Strain

Acute chagasic encephalitis is a clinically severe central nervous system (CNS) manifestation. However, the knowledge of the nervous form of Chagas disease is incomplete. The role of the muscarinic acetylcholine receptor (mAChR) on mice behavior and brain lesions induced by <i>Trypanosoma cruz...

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Main Authors: Gabriela Maira Pereira de Assis, Micheline Freire Donato, Matheus Marques Milagre, Samantha Ribeiro Béla, Mayra Fernanda Ricci, Luara Augusta Batista, Maria Elena de Lima, Fabrício de Araujo Moreira, Rosa Maria Esteves Arantes, Marta de Lana
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Pathogens
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Online Access:https://www.mdpi.com/2076-0817/10/2/121
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author Gabriela Maira Pereira de Assis
Micheline Freire Donato
Matheus Marques Milagre
Samantha Ribeiro Béla
Mayra Fernanda Ricci
Luara Augusta Batista
Maria Elena de Lima
Fabrício de Araujo Moreira
Rosa Maria Esteves Arantes
Marta de Lana
author_facet Gabriela Maira Pereira de Assis
Micheline Freire Donato
Matheus Marques Milagre
Samantha Ribeiro Béla
Mayra Fernanda Ricci
Luara Augusta Batista
Maria Elena de Lima
Fabrício de Araujo Moreira
Rosa Maria Esteves Arantes
Marta de Lana
author_sort Gabriela Maira Pereira de Assis
collection DOAJ
description Acute chagasic encephalitis is a clinically severe central nervous system (CNS) manifestation. However, the knowledge of the nervous form of Chagas disease is incomplete. The role of the muscarinic acetylcholine receptor (mAChR) on mice behavior and brain lesions induced by <i>Trypanosoma cruzi</i> (Colombian strain) was herein investigated in mice treated with the mAChR agonist and antagonist (carbachol and atropine), respectively. Immunosuppressed or non-immunosuppressed mice were intracerebroventricularly (icv) or intraperitoneally (ip) infected. All groups were evaluated 15 d.p.i. (days post infection). Intraperitoneally infected animals had subpatent parasitemia. Patent parasitemia occurred only in icv infected mice. The blockade of mAChR increased the parasitemia, parasitism and lesions compared to its activation. Infected not treated (INT ip) mice did not present meningitis and encephalitis, regardless of immunosuppression. INT icv brains presented higher cellularity, discrete signs of cellular degeneration, frequent presence of parasites and focal meningitis. The immunosuppressed atropine + icv mice presented increased intracellular parasitism associated with degenerative parenchymal changes, while carbachol + icv mice presented discrete meningitis, preservation of the cortex and absence of relevant parasitism. Cholinergic receptor blockage increased impairment of coordination vs. receptor activation. Muscarinic cholinergic pathway seems to be involved in immune mediated cell invasion events while its blockade favored infection evolution, brain lesions, and behavioral alterations.
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spelling doaj.art-aad4a0ecf0ef4a9aa5812ffdfeb28dda2023-12-03T14:33:10ZengMDPI AGPathogens2076-08172021-01-0110212110.3390/pathogens10020121Participation of Central Muscarinic Receptors on the Nervous Form of Chagas Disease in Mice Infected via Intracerebroventricular with Colombian <i>Trypanosoma cruzi</i> StrainGabriela Maira Pereira de Assis0Micheline Freire Donato1Matheus Marques Milagre2Samantha Ribeiro Béla3Mayra Fernanda Ricci4Luara Augusta Batista5Maria Elena de Lima6Fabrício de Araujo Moreira7Rosa Maria Esteves Arantes8Marta de Lana9Programa de Pós-Graduação em Ciências Biológicas (CBIOL), Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto (UFOP), 35400-000 Ouro Preto, BrazilPrograma de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos (PGPNSB), Universidade Federal da Paraíba (UFPB), 58010-340 João Pessoa, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas (CiPHARMA), Escola de Farmácia, Universidade Federal de Ouro Preto (UFOP), 35400-000 Ouro Preto, BrazilPrograma de Pós-Graduação em Ciências Biológicas (CBIOL), Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto (UFOP), 35400-000 Ouro Preto, BrazilDepartamento de Patologia Geral, Instituto de Ciências Biológicas (ICB), Universidade Federal de Minas Gerais (UFMG), 31660-060 Belo Horizonte, BrazilPrograma de Pós Graduação em Neurociência, Departamento de Farmacologia, Instituto de Ciências Biológicas (ICB), Universidade Federal de Minas Gerais (UFMG), 31660-060 Belo Horizonte, BrazilSanta Casa de Belo Horizonte: Instituto de Ensino e Pesquisa, 30150-240 Belo Horizonte, BrazilPrograma de Pós Graduação em Neurociência, Departamento de Farmacologia, Instituto de Ciências Biológicas (ICB), Universidade Federal de Minas Gerais (UFMG), 31660-060 Belo Horizonte, BrazilDepartamento de Patologia Geral, Instituto de Ciências Biológicas (ICB), Universidade Federal de Minas Gerais (UFMG), 31660-060 Belo Horizonte, BrazilPrograma de Pós-Graduação em Ciências Biológicas (CBIOL), Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto (UFOP), 35400-000 Ouro Preto, BrazilAcute chagasic encephalitis is a clinically severe central nervous system (CNS) manifestation. However, the knowledge of the nervous form of Chagas disease is incomplete. The role of the muscarinic acetylcholine receptor (mAChR) on mice behavior and brain lesions induced by <i>Trypanosoma cruzi</i> (Colombian strain) was herein investigated in mice treated with the mAChR agonist and antagonist (carbachol and atropine), respectively. Immunosuppressed or non-immunosuppressed mice were intracerebroventricularly (icv) or intraperitoneally (ip) infected. All groups were evaluated 15 d.p.i. (days post infection). Intraperitoneally infected animals had subpatent parasitemia. Patent parasitemia occurred only in icv infected mice. The blockade of mAChR increased the parasitemia, parasitism and lesions compared to its activation. Infected not treated (INT ip) mice did not present meningitis and encephalitis, regardless of immunosuppression. INT icv brains presented higher cellularity, discrete signs of cellular degeneration, frequent presence of parasites and focal meningitis. The immunosuppressed atropine + icv mice presented increased intracellular parasitism associated with degenerative parenchymal changes, while carbachol + icv mice presented discrete meningitis, preservation of the cortex and absence of relevant parasitism. Cholinergic receptor blockage increased impairment of coordination vs. receptor activation. Muscarinic cholinergic pathway seems to be involved in immune mediated cell invasion events while its blockade favored infection evolution, brain lesions, and behavioral alterations.https://www.mdpi.com/2076-0817/10/2/121nervous Chagas diseasemuscarinic cholinergic pathwayinfection evolution
spellingShingle Gabriela Maira Pereira de Assis
Micheline Freire Donato
Matheus Marques Milagre
Samantha Ribeiro Béla
Mayra Fernanda Ricci
Luara Augusta Batista
Maria Elena de Lima
Fabrício de Araujo Moreira
Rosa Maria Esteves Arantes
Marta de Lana
Participation of Central Muscarinic Receptors on the Nervous Form of Chagas Disease in Mice Infected via Intracerebroventricular with Colombian <i>Trypanosoma cruzi</i> Strain
Pathogens
nervous Chagas disease
muscarinic cholinergic pathway
infection evolution
title Participation of Central Muscarinic Receptors on the Nervous Form of Chagas Disease in Mice Infected via Intracerebroventricular with Colombian <i>Trypanosoma cruzi</i> Strain
title_full Participation of Central Muscarinic Receptors on the Nervous Form of Chagas Disease in Mice Infected via Intracerebroventricular with Colombian <i>Trypanosoma cruzi</i> Strain
title_fullStr Participation of Central Muscarinic Receptors on the Nervous Form of Chagas Disease in Mice Infected via Intracerebroventricular with Colombian <i>Trypanosoma cruzi</i> Strain
title_full_unstemmed Participation of Central Muscarinic Receptors on the Nervous Form of Chagas Disease in Mice Infected via Intracerebroventricular with Colombian <i>Trypanosoma cruzi</i> Strain
title_short Participation of Central Muscarinic Receptors on the Nervous Form of Chagas Disease in Mice Infected via Intracerebroventricular with Colombian <i>Trypanosoma cruzi</i> Strain
title_sort participation of central muscarinic receptors on the nervous form of chagas disease in mice infected via intracerebroventricular with colombian i trypanosoma cruzi i strain
topic nervous Chagas disease
muscarinic cholinergic pathway
infection evolution
url https://www.mdpi.com/2076-0817/10/2/121
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