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Published on: June 8, 2017
Cerebral Malaria Causes Enduring Behavioral and Molecular Changes in Mice Brain Without Causing Gross
Thaíze Lopes de Souza1, Ana Claudia Beck Grauncke1, Leandro Rodrigo Ribeiro1
1Graduate Program in Pharmacology and Department of Physiology and Pharmacology, Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil.
Cerebral malaria (CM) survivors show lasting behavioral and neurochemical changes, including impaired natural behaviors and altered brain chemistry, even after infection clearance. These persistent effects highlight the need for new therapeutic strategies for CM sequelae.
Area of Science:
- Neuroscience
- Parasitology
- Pathology
Background:
- Malaria is a significant global health issue caused by Plasmodium parasites.
- Cerebral malaria (CM) is a severe form of malaria with high mortality and potential for long-term cognitive deficits.
- Existing treatments do not fully address the persistent sequelae of CM.
Purpose of the Study:
- To investigate persistent behavioral, neurochemical, and neuropathological changes after experimental cerebral malaria (CM) in mice.
- To understand the molecular mechanisms underlying long-term deficits following CM recovery.
- To identify potential therapeutic targets for CM sequelae.
Main Methods:
- Experimental cerebral malaria induced by P. berghei ANKA in C57BL/6 mice.
- Behavioral assessments including nest building and marble burying tests.
- Neurochemical analyses: Na+,K+-ATPase activity, benzodiazepine/GABA(A) receptor binding, and protein oxidative damage markers.
- Neuropathological assessments using Fluoro-Jade C, Timm staining, and IBA-1.
Main Results:
- Persistent alterations in natural behaviors (impaired nest building, increased marble burying) were observed post-CM.
- Neurochemical changes included decreased Na+,K+-ATPase activity, altered phosphorylated Na+,K+-ATPase immunoreactivity, and reduced benzodiazepine/GABA(A) receptor binding.
- Evidence of oxidative damage to proteins in the hippocampus was found, while key neuropathological markers remained unchanged.
- No significant changes were detected in Fluoro-Jade C, Timm staining, or IBA-1.
Conclusions:
- Behavioral and neurochemical alterations persist in mice even after clearance of parasitemia and recovery from experimental CM.
- These findings align with clinical observations of enduring cognitive deficits in human CM survivors.
- The identified molecular alterations may contribute to persistent behavioral changes and seizure susceptibility, offering insights for future therapeutic development.
