Abstract
BackgroundCerebral malaria, the main complication of Plasmodium falciparum infection in humans, is associated with persistent neurocognitive sequels both in human disease and the murine experimental model. In recent years, cognitive deficits related to uncomplicated (non-cerebral) malaria have also been reported in chronically exposed residents of endemic areas, but not in some murine experimental models of non-cerebral malaria. This study aimed at evaluating the influence of uncomplicated malaria on different behavioural paradigms associated with memory and anxiety-like parameters in a murine model that has the ability to develop cerebral malaria.MethodsPlasmodium berghei ANKA-infected and non-infected C57BL/6 mice were used. Development of cerebral malaria was prevented by chloroquine treatment starting on the fourth day of infection. The control group (non-infected mice) were treated with PBS. The effect of uncomplicated malaria infection on locomotor habituation, short and long-term memory and anxious-like behaviour was evaluated 64 days after parasite clearance in assays including open field, object recognition, Y-maze and light/dark tasks.ResultsPlasmodium berghei ANKA-infected mice showed significant long-lasting disturbances reflected by a long-term memory-related behaviour on open field and object recognition tasks, accompanied by an anxious-like phenotype availed on open field and light-dark tasks.ConclusionsLong-term neurocognitive sequels may follow an uncomplicated malaria episode in an experimental model prone to develop cerebral malaria, even if the infection is treated before the appearance of clinical signs of cerebral impairment.
Highlights
Cerebral malaria, the main complication of Plasmodium falciparum infection in humans, is associated with persistent neurocognitive sequels both in human disease and the murine experimental model
To address whether uncomplicated P. berghei ANKA (PbA) malaria might influence different behavioural paradigms two months after infection and treatment, C57BL/6 mice were inoculated with 106 parasitized erythrocytes and treated with CQ for seven days from day 4 of infection (Fig. 1)
Effect of CQ treatment on parasitaemia and on recognition memory or anxiety in mice None of the animals treated with CQ for 7 days showed recrudescence of parasitaemia for up to 4 months of follow-up (Fig. 2) and this therapeutic scheme alone did Effect of uncomplicated malaria on locomotor activity PbA infected/treated mice showed no difference in the total distance travelled in both Open Field task (OFT) paradigms in relation to the control group (both groups; ANOVA: F(1, 80) = 52.36, P < 0.0001, Fig. 4a)
Summary
The main complication of Plasmodium falciparum infection in humans, is associated with persistent neurocognitive sequels both in human disease and the murine experimental model. Poor performance in cognitive events, mainly related to learning and memory, has been observed in individuals with uncomplicated malaria episodes in different endemic regions of the world [14,15,16,17,18]. They were not, observed in some murine experimental models in which CM is not expected to occur [12, 19]. The appearance of CM in some models seems, to depend on the host-parasite interaction specific to each situation, involving the genetic background of the host and the parasite species and strains and the nature and intensity of the consequent inflammatory response, determining or not damage to brain tissues and vasculature [20]
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