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Increased c-fos expression in the brain during experimental murine cerebral malaria: possible association with
N Ma1, A J Harding, R Pamphlett
1Department of Pathology, University of Sydney, NSW, Australia.
Abstract:
Cerebral expression of c-fos protein was studied by immunocytochemistry in murine cerebral malaria (CM) and malaria without cerebral involvement (non-CM). c-fos expression, low in the brains of uninfected mice, increased in frequency, intensity, and distribution during the course of fatal CM (e.g., a 70-fold increase on day 7 after inoculation). These changes paralleled the timing and degree of the neurologic complications and histopathologic changes. Only a slight increase in c-fos expression was detectable in non-CM mice on day 7 after inoculation. Dexamethasone treatment (days 0 and 1 after inoculation) of the CM mice largely prevented the increased cerebral c-fos expression, histopathologic changes, cerebral complications, and death. Increased c-fos expression may indicate the specific neuronal pathways activated by the immunopathologic process of fatal murine CM and could be associated with the behavioral changes and neurologic complications in this model.
Insights
Cerebral malaria (CM) in mice significantly increases c-fos protein expression in the brain, correlating with neurological damage. Dexamethasone treatment reduced these changes, suggesting c-fos activation is linked to CM pathology.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection.
- The underlying neuropathology of CM remains incompletely understood.
- Neuronal activation markers may provide insights into CM pathogenesis.
Purpose of the Study:
- To investigate the cerebral expression of c-fos protein in a murine model of CM.
- To correlate c-fos expression with neurological complications and histopathology in CM.
- To assess the effect of dexamethasone on c-fos expression and CM progression.
Main Methods:
- Immunocytochemistry was used to detect c-fos protein expression in the brains of infected and uninfected mice.
- Mice were categorized into cerebral malaria (CM) and non-cerebral malaria (non-CM) groups.
- Dexamethasone treatment was administered to a subset of CM mice.
Main Results:
- Fatal CM exhibited a significant, time-dependent increase in c-fos expression (up to 70-fold) in the brain.
- Increased c-fos expression paralleled the severity of neurological deficits and brain tissue damage in CM.
- Non-CM mice showed only a minor increase in c-fos expression.
- Dexamethasone treatment attenuated c-fos upregulation, histopathological changes, neurological complications, and mortality in CM mice.
Conclusions:
- Elevated cerebral c-fos expression is a hallmark of fatal murine CM.
- c-fos activation likely reflects neuronal pathways involved in the immunopathogenesis of CM.
- These findings suggest a link between c-fos expression and the neurological manifestations of CM.