Abstract
Malaria, a mosquito-borne disease caused by Plasmodium spp. is considered to be a global threat, specifically for the developing countries. In human subjects considerable information exists regarding post-malarial physiology. However, most murine malarial models are lethal, and most studies deal with acute phases occurring as disease progresses. Much less is known regarding physiological status post-parasite clearance. We have assessed the physiological changes at the organ levels using 1H NMR based metabonomics in a non lethal self-clearing murine malarial model of P. chabaudi parasites and Balb/C, far beyond the parasite clearance point. The results showed distinct metabolic states between uninfected and infected mice at the peak parasitemia, as well as three weeks post-parasite clearance. Our data also suggests that the response at the peak infection as well as recovery exhibited distinct sexual dimorphism. Specifically, we observed accumulation of acetylcholine in the brain metabolic profile of both the sexes. This might have important implication in understanding the pathophysiology of the post malarial neurological syndromes. In addition, the female liver showed high levels of glucose, dimethylglycine, methylacetoacetate and histidine after three weeks post-parasite clearance, while the males showed accumulation of branched chain amino acids, lysine, glutamine and bile acids.
Highlights
Malaria is caused by the five species of Plasmodium, namely, P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi [1]
We have studied the alterations in the metabolome of liver, brain and serum during infection and recovery of Balb/C mice infected with Plasmodium chabaudi
This model of malaria has been of particular interest because of its non-lethality and resemblance to non-lethal human malarial infection caused by P. falciparum and P. vivax [24]
Summary
Malaria is caused by the five species of Plasmodium, namely, P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi [1]. The infection may or may not affect the central nervous system. Recovery from the malarial parasite infection may alter the host physiology significantly. It is important to understand the organ level physiological events which are known to control and/or are affected during the recovery from the disease. We report the metabolic changes during the peak infection stage and post-parasite clearance compared to healthy animals in a non-lethal murine model of the disease. Using Balb/C mice infected with P. chabaudi. Our data suggests that the recovered mice exhibit specific physiological differences from that of the healthy control mice. The mode of physiological changes during peak infection as well as recovery is distinctly different in male and female mice
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