期刊
PATHOGENS
卷 10, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/pathogens10020121
关键词
nervous Chagas disease; muscarinic cholinergic pathway; infection evolution
类别
资金
- Brazilian agency CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) [431413/2016-9, 311568/2020-3, 402653/2018-1]
- Brazilian agency FAPEMIG (Fundacao de Amparo a Pesquisa do Estado de Minas Gerais) [APQ-01160-15, APQ-00766-16, PPM-00304-16, APQ-01781-17, APQ-00921-18]
- Brazilian agency CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)
The study found that the nervous form of Chagas disease is associated with brain lesions and behavioral changes, which are affected by the muscarinic acetylcholine receptor (mAChR) activation or blockade. Blocking the mAChR was found to promote infection evolution and brain damage, while activation helped maintain brain tissue integrity.
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 Trypanosoma cruzi (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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据