Abstract
A significant fraction of global population is under the threat of malaria. Majority of annual death is due to the more complicated form of the infection i.e. the cerebral form, also known as Cerebral Malaria (CM). Host parasite interaction is known to cause a cascade of events in various tissues like brain, liver, kidney, and spleen. We have employed 1H NMR based metabolomics to understand the specific perturbations of various tissues in CM. In our previous paper we have delineated the differences between CM vis-a-vis non-cerebral malaria (NCM) mice in serum, liver and brain. In this paper we focus on their differences of metabolic profile in kidney and spleen as kidney dysfunction and splenomegaly are known to be associated to neurological outcome of the disease. Moreover we have also looked into how the biological compartments (kidney, spleen and serum) interact with each other. The various metabolites involved in such interactions and their correlational aspects across the compartments have been studied in CM, NCM and control mice. The idea was to find out the specific pathways that are altered in CM mice. Our results demonstrate that both the kidney as well as spleen metabolism are differentially perturbed in CM with respect to NCM. The results point out that glutamate levels are decreased in CM mice with respect to NCM mice both in case of spleen and kidney while creatine, myo-inositol and betaine levels are increased in kidney of CM mice with respect to NCM mice. From the analysis of Multiway Principal Component Analysis (MPCA) we see that lipid metabolism and TCA cycle is altered in kidney and spleen.
Highlights
Cerebral malaria (CM) is one of the complicated forms of malaria and the neurological outcome of this disease is often correlated to the dysfunction of liver [1], brain [2,3,4], acute renal failure [5,6,7] and splenomegaly [8,9,10]
It is known that C57BL/6 infected with PbA is a model of experimental cerebral malaria [33,34]
Eight mice transited to the cerebral form of the disease while nine of them remained non-cerebral malaria (NCM), four mice were found dead during night and were not considered in the analysis
Summary
Cerebral malaria (CM) is one of the complicated forms of malaria and the neurological outcome of this disease is often correlated to the dysfunction of liver [1], brain [2,3,4], acute renal failure [5,6,7] and splenomegaly [8,9,10]. These are some of its serious complications which could be life threatening. We focus on the alterations in spleen and kidney
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