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

• Published in: Pathogens (Basel) 2021-01, Vol.10 (2), p.121
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Acetylcholine receptors; Acetylcholine receptors (muscarinic); Animals; Asymptomatic; Atropine; Brain; Carbachol; Cardiomyopathy; Central nervous system; Chagas disease; Cholinergics; Degeneration; Encephalitis; Immunosuppression; infection evolution; Infections; Lesions; Meningitis; Mortality; muscarinic cholinergic pathway; nervous Chagas disease; Nervous system; Neurodegeneration; Parasitemia; Parasites; Parasitism; Physiology; Receptor mechanisms; Receptors; Trypanosoma cruzi; Vector-borne diseases
• ISSN: 2076-0817; 2076-0817
• 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.