de Assis Gabriela Maira Pereira, Donato Micheline Freire, Milagre Matheus Marques, Béla Samantha Ribeiro, Ricci Mayra Fernanda, Batista Luara Augusta, de Lima Maria Elena, Moreira Fabrício de Araujo, Arantes Rosa Maria Esteves, de Lana Marta
Programa de Pós-Graduação em Ciências Biológicas (CBIOL), Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto (UFOP), 35400-000 Ouro Preto, Brazil.
Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos (PGPNSB), Universidade Federal da Paraíba (UFPB), 58010-340 João Pessoa, Brazil.
Pathogens. 2021 Jan 25;10(2):121. doi: 10.3390/pathogens10020121.
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 (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.
急性恰加斯病性脑炎是一种临床严重的中枢神经系统（CNS）表现。然而，关于恰加斯病神经型的知识并不完整。本文分别在用毒蕈碱型乙酰胆碱受体（mAChR）激动剂和拮抗剂（卡巴胆碱和阿托品）处理的小鼠中，研究了mAChR对由（哥伦比亚株）诱导的小鼠行为和脑损伤的作用。免疫抑制或未免疫抑制的小鼠通过脑室内（icv）或腹腔内（ip）感染。所有组在感染后15天（d.p.i.）进行评估。腹腔内感染的动物有亚临床寄生虫血症。仅脑室内感染的小鼠出现明显的寄生虫血症。与激活mAChR相比，阻断mAChR会增加寄生虫血症、寄生现象和损伤。未治疗的感染（INT ip）小鼠无论是否免疫抑制均未出现脑膜炎和脑炎。INT icv组的脑呈现更高的细胞密度、离散的细胞变性迹象、频繁出现的寄生虫和局灶性脑膜炎。免疫抑制的阿托品 + icv组小鼠出现与实质性变性改变相关的细胞内寄生现象增加，而卡巴胆碱 + icv组小鼠出现离散性脑膜炎、皮质保存且无明显寄生现象。胆碱能受体阻断相对于受体激活会增加协调功能损害。毒蕈碱胆碱能途径似乎参与免疫介导的细胞侵袭事件，而其阻断有利于感染进展、脑损伤和行为改变。
