Abstract
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.
Highlights
Chagas disease (CD) or American Trypanosomiasis is a complex anthropozoonosis caused by the protozoan hemoflagellate Trypanosoma cruzi (T. cruzi), naturally transmitted to vertebrate hosts by the elimination of metacyclic trypomastigotes forms in the feces and/or urine of triatomine vectors belonging to the family Reduviidae and subfamily Triatominae [1,2]
The central nervous system (CNS) impairment is recognized only at the acute phase, when meningoencephalitis presents as an important cause of death [5,6]
No statistical differences were observed in parasitemia among all groups when evaluated up 15 d.p.i. (Figure 1A), but the rate of mortality of the animals of the inoculated via icv and not treated (INT icv) (40%) was significantly higher (p < 0.05) than INT ip group (0%) (Figure 1C and Table 1)
Summary
Chagas disease (CD) or American Trypanosomiasis is a complex anthropozoonosis caused by the protozoan hemoflagellate Trypanosoma cruzi (T. cruzi), naturally transmitted to vertebrate hosts by the elimination of metacyclic trypomastigotes forms in the feces and/or urine of triatomine vectors belonging to the family Reduviidae and subfamily Triatominae [1,2]. CD represents a new global challenge due to its expansion for non-endemic countries due to the migration of infected individuals, where the parasite continues to be transmitted by mechanisms independent of the insect vector [4] This disease presents two distinct phases, the initial acute phase that may be asymptomatic, oligosymptomatic or symptomatic with severe and fatal manifestations in children up to four years old or in immunosuppressed individuals. In most patients with the symptomatic acute nervous form, the lesions, parasitism, and all manifestations, including neurological signs and symptoms, disappear spontaneously without apparent sequelae [15], what reinforces the view against the existence of a chronic nervous form of CD [9,15,16] These observations lead to be ignored the nervous form of the CD. Peripheral nervous system (PNS) alterations are better understood, and dysautonomia secondary to ganglia and nerve endings of the sympathetic and parasympathetic autonomic nervous system have been consistently implicated in the pathophysiology of cardiomyopathy and chagasic megasyndromes [8,20]
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