Behavioural alterations are independent of sickness behaviour in chronic experimental Chagas disease

Abstract

The existence of the nervous form of Chagas disease is a matter of discussion since Carlos Chagas described neurological disorders, learning and behavioural alterations in Trypanosoma cruzi-infected individuals. In most patients, the clinical manifestations of the acute phase, including neurological abnormalities, resolve spontaneously without apparent consequence in the chronic phase of infection. However, chronic Chagas disease patients have behavioural changes such as psychomotor alterations, attention and memory deficits, and depression. In the present study, we tested whether or not behavioural alterations are reproducible in experimental models. We show that C57BL/6 mice chronically infected with the Colombian strain of T. cruzi (150 days post-infection) exhibit behavioural changes as (i) depression in the tail suspension and forced swim tests, (ii) anxiety analysed by elevated plus maze and open field test sand and (iii) motor coordination in the rotarod test. These alterations are neither associated with neuromuscular disorders assessed by the grip strength test nor with sickness behaviour analysed by temperature variation sand weight loss. Therefore, chronically T. cruzi-infected mice replicate behavioural alterations (depression and anxiety) detected in Chagas disease patients opening an opportunity to study the interconnection and the physiopathology of these two biological processes in an infectious scenario.

Memory impairment in chronic experimental Chagas disease: Benznidazole therapy reversed cognitive deficit in association with reduction of parasite load and oxidative stress in the nervous tissue

“…To approach our questions, C57BL/6 mice were infected with low inoculum of blood trypomastigotes of the Colombian type I T . cruzi strain, which allowed immune response to control parasite, host survival and development of the chronic phase of infection [ 18 , 22 ]. Further, in comparison with age-matched non-infected controls, chronically infected mice did not display neuromuscular disorders assessed by grip strength meter test, and, therefore, suitable as an experimental model to address our issues.…”

“…Previously, we have described that in chronically T . cruzi -infected C57BL/6 mice depressive-like behavior, anxiety and motor coordination disorder occur independently of sickness behavior and neuromuscular disorder [ 17 , 18 ]. The present study was carried out to evaluate the presence of memory impairment in chronically T .…”

Mexican Medicinal Plants as an Alternative for the Development of New Compounds Against Protozoan Parasites

“…The acute phase lasts for the first few weeks or months of infection; it can be asymptomatic or include fever, fatigue, and local swelling (called chagoma). In the chronic phase, patients usually have cardiac abnormalities, as well as digestive, neurological, or mixed alterations; recently, it has been shown that they also have behavioral changes, such as psychomotor alterations, attention and memory deficits, as well as depression [52]. Chemotherapy involves the use of two drugs: nifurtimox and benznidazole.…”

Shared neuroimmune and oxidative pathways underpinning Chagas disease and major depressive disorder

“…Nevertheless, in some cases, this indeterminate form is followed by symptomatic forms of the chronic phase, characterized by decrease in parasitemia and by cardiac, digestive or neurological manifestations 1,11 . Moreover, some preclinical and clinical studies reported that, in the chronic phase of CD, there are behavioral changes and the occurrence of psychiatric comorbidities such as anxiety and depression, conditions that, in principle, cannot solely be explained by the psychological status of the patient [12][13][14][15][16][17][18] .…”