Relation between acetylcholinesterase and Na+, K+-ATPase activities with impaired memory of mice experimentally infected by Trypanosoma cruzi.

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and causes severe cardiac and brain damage, leading to behavioral alterations in humans and animals. However, the mechanisms involved in memory impairment during T. cruzi infection remain unknown. It has long been recognized that the enzymatic activities of acetylcholinesterase (AChE) and Na+, K+-ATPase are linked with memory dysfunction during other trypanosomiasis. Thus, the aim of this study was to evaluate the involvement of cerebral AChE and Na+, K+-ATPase activities in the memory impairment during T. cruzi (Colombian strain) infection. A significant decrease on latency time during the inhibitory avoidance task was observed in animals infected by T. cruzi compared to uninfected animals, findings compatible to memory dysfunction. Moreover, the cerebral AChE activity increased, while the Na+, K+-ATPase decreased in T. cruzi infected compared to uninfected animals. Histopathology revealed mild to moderate multifocal gliosis in the cerebral cortex and light focal meningeal lymphoplasmacytic infiltrate, which may have contributed to memory loss. Based on these evidences, we can conclude that T. cruzi (Colombian strain) causes memory impairment in mice experimentally infected. Moreover, the changes in AChE and Na+, K+-ATPase activities may be considered a mechanism involved in disease pathogenesis.

Relationship between behavioral alterations and activities of adenylate kinase and creatine kinase in brain of rats infected by Trypanosoma evansi.

The aim of this study was to investigate the behavioral assessment and activities of important enzymes involved in the phosphoryl transfer network in rat brains that were experimentally infected with Trypanosoma evansi. Behavioral assessment (cognitive performance), pro-inflammatory cytokines in serum and activities of adenylate kinase (AK), pyruvate kinase (PK), and creatine kinase (CK) in brain were evaluated at 5 and 15 days post-infection (PI). Here we demonstrate a cognitive impairment in the rats infected with T. evansi. At 5 and 15 days PI, a memory deficit and a depressant activity were demonstrated by an inhibition avoidance test and increase in the immobility time in a tail suspension test, respectively. On day 5 PI, a decrease in the CK activity and an increase in the AK activity were observed. On day 15 PI, an increase in the CK activity and a decrease in the AK activity were observed. Considering the importance of energy metabolism for brain functioning, it is possible that the changes in the activity of enzymes involved in the cerebral phosphotransfer network and an increase in the proinflammatory cytokines (TNF and IFN) may be involved at least in part in the cognitive impairment in infected rats with T. evansi.

Nerolidol-loaded nanospheres prevent behavioral impairment via ameliorating Na+, K+-ATPase and AChE activities as well as reducing oxidative stress in the brain of Trypanosoma evansi-infected mice.

The aim of this study was to investigate the effect of nerolidol-loaded nanospheres (N-NS) on the treatment of memory impairment caused by Trypanosoma evansi in mice, as well as oxidative stress, and Na+, K+-ATPase and acetylcholinesterase (AChE) activities in brain tissue. Animals were submitted to behavioral tasks (inhibitory avoidance task and open-field test) 4 days postinfection (PI). Reactive oxygen species (ROS) and thiobarbituric acid-reactive substance (TBARS) levels and catalase (CAT), superoxide dismutase (SOD), Na+, K+-ATPase and AChE activities were measured on the fifth-day PI. T. evansi-infected mice showed memory deficit, increased ROS and TBARS levels and SOD and AChE activities, and decreased CAT and Na+, K+-ATPase activities compared to uninfected mice. N-NS prevented memory impairment and oxidative stress parameters (except SOD activity), while free nerolidol (N-F) restored only CAT activity. Also, N-NS treatment was able to prevent alterations in Na+, K+-ATPase and AChE activities caused by T. evansi infection. A significantly negative correlation was observed between memory and ROS production (p < 0.001; r = -0.941), as well as between memory and AChE activity (p < 0.05; r = -0.774). On the contrary, a significantly positive correlation between memory and Na+, K+-ATPase activity was observed (p < 0.01; r = 0.844). In conclusion, N-NS was able to reverse memory impairment and to prevent increased ROS and TBARS levels due to amelioration of Na+, K+-ATPase and AChE activities and to activation of the antioxidant enzymes, respectively. These results suggest that N-NS treatment may be a useful strategy to treat memory dysfunction and oxidative stress caused by T. evansi infection.

Neuropsychiatric manifestations of some tropical diseases.

Some tropical diseases are the direct cause of severe disturbances of cerebral function while others affect only finer cerebral systems controlling fears, anxiety and personality traits. The mechanisms by which psychiatric symptoms are produced in tropical disorders are not any different from the mechanisms that relate to any physical disorders. Neuropsychiatric symptoms may be caused by a number of different mechanisms including bacterial toxins, release of cytokines, hyperthermia, shock (poor perfusion), acute renal insufficiency, pulmonary failure (shock lung), coagulopathy, disruption of the blood-brain barrier, and/or the nest of pathogens into the central nervous system. The following tropical illnesses can be associated with neuropsychiatric symptoms: neurocysticercosis, malaria, trypanosomiasis, dengue, and schistosomiasis. Neurological and psychiatric impairments induced by tropical diseases both represent a major category of invalidating disorders, which cause profound changes in the nervous system functions, often associated with severe sequels or late-onset disturbances. It is therefore important to disseminate knowledge of the neuropsychiatric symptoms accompanying tropical diseases in order to increase the awareness of these problems and challenges.

[Clinical, parasitological and histopathologic follow-up studies of acute Chagas patients treated with benznidazole]. / Seguimiento clínico, parasitológico e histopatológico de pacientes chagásicos agudos tratados con benznidazol.

With the purpose of studying their clinical and histopathologic evolution, 10 acute chagasic patients with myocarditis diagnosed by endomyocardial biopsy and positive sero-parasitologic methods were evaluated at 11 months (8-21 months) after treatment with oral benznidazole. Four of them were reevaluated 5 years post-treatment (58-68 months). Study protocol consisted of clinical, hemodynamic, echocardiographic, seroparasitologic and histopathologic evaluations. Results showed evidence of persisting myocarditis in 90% and 75% of patients evaluated at 11 months and 5 years respectively, along with asymptomatic, subclinical left ventricular systolic dysfunction being recognized in 75% of patients evaluated 5 years after treatment. All parasitologic studies became negative during follow-up, but serology remained positive for Trypanosoma cruzi antibodies in 80% and 75% of patients studied at 11 months and 5 years. In conclusion, myocardial damage was constantly found in our acute chagasic patients. Treatment with benznidazole eliminated symptoms and parasitemia, but it does not seem to alter favorably the histopathological evolution of the chagasic cardiac disease.