title: Metabolic fingerprints of serum, brain, and liver are distinct for mice with cerebral and noncerebral malaria: a ¹H NMR spectroscopy-based metabonomic study.
abstract: Cerebral malaria (CM) is a life-threatening disease in humans caused by Plasmodium falciparum, leading to high mortality. Plasmodium berghei ANKA (PbA) infection in C57Bl/6 mice induces pathologic symptoms similar to that in human CM. However, experimental CM incidence in mice is variable, and there are no known metabolic correlates/fingerprints for the animals that develop CM. Here, we have used (1)H NMR-based metabonomics to investigate the metabolic changes in the mice with CM with respect to the mice that have noncerebral malaria (NCM) of the same batchmates with identical genetic backgrounds and infected simultaneously. The metabolic profile of the infected mice (both CM and NCM) was separately compared with the metabolite profile of uninfected control mice of same genetic background. The objective of this study was to search for metabolic changes/fingerprints of CM and identify the pathways that might be differentially altered in mice that succumbed to CM. The results show that brain, liver, and sera exhibit unique metabolic fingerprints for CM over NCM mice. Some of the major fingerprints are increased level of triglycerides, VLDL-cholesterol in sera of CM mice, and decreased levels of glutamine in the sera concomitant with increased levels of glutamine in the brain of the mice with CM. Moreover, glycerophosphocholine is decreased in both the brain and the liver of animals with CM, and myo-inositol and histamine are increased in the liver of CM mice. The metabolic fingerprints in brain, sera, and liver of mice with CM point toward perturbation in the ammonia detoxification pathway and perturbation in lipid and choline metabolism in CM specifically. The study helps us to understand the severity of CM over NCM and in unrevealing the specific metabolic pathways that are compromised in CM.
authors: Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400005, India.
authors: Soumita
authors: S
authors: Ghosh
authors: Arjun
authors: A
authors: Sengupta
authors: Shobhona
authors: S
authors: Sharma
authors: Haripalsingh M
authors: HM
authors: Sonawat
mesh_terms: D000641:Ammonia / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000378:metabolism* / Q000469:parasitology; D005260:Female; D005947:Glucose / Q000378:metabolism; D006790:Host-Parasite Interactions; D007294:Inositol / Q000378:metabolism; D016018:Least-Squares Analysis; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism* / Q000469:parasitology; D009682:Magnetic Resonance Spectroscopy; D008288:Malaria / Q000097:blood / Q000378:metabolism / Q000469:parasitology; D016779:Malaria, Cerebral / Q000097:blood* / Q000378:metabolism / Q000469:parasitology; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D015999:Multivariate Analysis; D009928:Organ Specificity; D010962:Plasmodium berghei / Q000502:physiology*; D025341:Principal Component Analysis; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; D008055:Lipids; D007294:Inositol; D000641:Ammonia; D005947:Glucose