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Chagas disease: modulation of the inflammatory response by acetylcholinesterase in hematological cells and brain
Aniélen D Silva1, Nathieli B Bottari1, Guilherme M do Carmo1
1Department of Biochemistry and Molecular Biology, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil.
Insights
Chagas disease infection in mice alters acetylcholinesterase activity and acetylcholine levels, activating the anti-inflammatory cholinergic pathway in the central nervous system.
Area of Science:
- Neuroimmunology
- Parasitology
- Pharmacology
Background:
- Chagas disease, caused by *Trypanosoma cruzi*, triggers severe inflammation.
- The inflammatory cholinergic pathway, regulated by acetylcholinesterase, influences acetylcholine levels, an anti-inflammatory mediator.
- Understanding the interplay between *T. cruzi* infection and this pathway is crucial for managing Chagas disease.
Purpose of the Study:
- To investigate the impact of *Trypanosoma cruzi* infection on acetylcholinesterase activity and acetylcholine levels in mice.
- To determine if these alterations are linked to the inflammatory cholinergic signaling pathway during acute Chagas disease.
Main Methods:
- Mice were infected with *T. cruzi* (Y strain) and compared to uninfected controls.
- Acetylcholinesterase activity, acetylcholine, and nitric oxide levels were measured in blood, lymphocytes, and brain.
- Myeloperoxidase activity and brain histopathology were analyzed to assess inflammation.
Main Results:
- Acetylcholinesterase activity decreased in blood and brain but increased in lymphocytes post-infection.
- *T. cruzi* infection elevated acetylcholine and nitric oxide levels in the brain.
- Increased myeloperoxidase activity and histopathological damage indicated heightened neuroinflammation.
Conclusions:
- Acute Chagas disease in mice induces significant alterations in the cholinergic system.
- Neuroinflammation in the central nervous system activates the anti-inflammatory cholinergic pathway.
- This study highlights the complex neuroimmune response during Chagas disease.
Abstract:
Chagas disease is an acute or chronic illness that causes severe inflammatory response, and consequently, it may activate the inflammatory cholinergic pathway, which is regulated by cholinesterases, including the acetylcholinesterase. This enzyme is responsible for the regulation of acetylcholine levels, an anti-inflammatory molecule linked to the inflammatory response during parasitic diseases. Thus, the aim of this study was to investigate whether Trypanosoma cruzi infection can alter the activity of acetylcholinesterase and acetylcholine levels in mice, and whether these alterations are linked to the inflammatory cholinergic signaling pathway. Twenty-four mice were divided into two groups: uninfected (control group, n = 12) and infected by T. cruzi, Y strain (n = 12). The animals developed acute disease with a peak of parasitemia on day 7 post-infection (PI). Blood, lymphocytes, and brain were analyzed on days 6 and 12 post-infection. In the brain, acetylcholine and nitric oxide levels, myeloperoxidase activity, and histopathology were analyzed. In total blood and brain, acetylcholinesterase activity decreased at both times. On the other hand, acetylcholinesterase activity in lymphocytes increased on day 6 PI compared with the control group. Infection by T. cruzi increased acetylcholine and nitric oxide levels and histopathological damage in the brain of mice associated to increased myeloperoxidase activity. Therefore, an intense inflammatory response in mice with acute Chagas disease in the central nervous system caused an anti-inflammatory response by the activation of the cholinergic inflammatory pathway.
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