Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry-Based Metabolomics Reveals Metabolic Alterations in the Mouse Cerebellum During Infection

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2020 Aug 9

PMID 32765450

Citations 6

Authors

Jun Ma

Jun-Jun He

Jun-Ling Hou

Chun-Xue Zhou

Hany M Elsheikha

Xing-Quan Zhu

Affiliations

Soon will be listed here.

Abstract

is a protozoan parasite with a remarkable neurotropism. We recently showed that infection can alter the global metabolism of the cerebral cortex of mice. However, the impact of infection on the metabolism of the cerebellum remains unknown. Here we apply metabolomic profiling to discover metabolic changes associated with infection of the mouse cerebellum using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Multivariate statistics revealed differences in the metabolic profiles between the infected and control mouse groups and between the infected mouse groups as infection advanced. We also detected 10, 22, and 42 significantly altered metabolites (SAMs) in the infected cerebellum at 7, 14, and 21 days post infection (dpi), respectively. Four metabolites [tabersonine, arachidonic acid (AA), docosahexaenoic acid, and oleic acid] were identified as potential biomarker or responsive metabolites to infection in the mouse cerebellum. Three of these metabolites (AA, docosahexaenoic acid, and oleic acid) play roles in the regulation of host behavior and immune response. Pathway analysis showed that infection of the cerebellum involves reprogramming of amino acid and lipid metabolism. These results showcase temporal metabolomic changes during cerebellar infection by in mice. The study provides new insight into the neuropathogenesis of infection and reveals new metabolites and pathways that mediate the interplay between and the mouse cerebellum.

Citing Articles

Altered landscape of total RNA, tRNA and sncRNA modifications in the liver and spleen of mice infected by Toxoplasma gondii.

Zhang X, Sun Y, Wang W, Gao Y, Wei X, Sun H PLoS Negl Trop Dis. 2024; 18(6):e0012281.

PMID: 38905319 PMC: 11221703. DOI: 10.1371/journal.pntd.0012281.

Observing astrocyte polarization in brains from mouse chronically infected with Toxoplasma gondii.

Yao Y, Yuan Y, Sheng S, Li Y, Tang X, Gu H Sci Rep. 2024; 14(1):10433.

PMID: 38714696 PMC: 11076485. DOI: 10.1038/s41598-024-60304-2.

Expression profiles of host miRNAs and circRNAs and ceRNA network during Toxoplasma gondii lytic cycle.

Wang S, Wang X, He J, Zheng W, Zhu X, Elsheikha H Parasitol Res. 2024; 123(2):145.

PMID: 38418741 PMC: 10902104. DOI: 10.1007/s00436-024-08152-x.

Behavioral and Neuropathological Changes After Ocular Conjunctival Infection in BALB/c Mice.

Soares G, de Leao E, Freitas S, Alves R, Tavares N, Costa M Front Cell Infect Microbiol. 2022; 12:812152.

PMID: 35372100 PMC: 8965508. DOI: 10.3389/fcimb.2022.812152.

Illuminating Host-Parasite Interaction at the Cellular and Subcellular Levels with Infrared Microspectroscopy.

Elsheikha H, Al-Sandaqchi A, Harun M, Winterton F, Altharawi A, Elsaied N Cells. 2022; 11(5).

PMID: 35269433 PMC: 8909495. DOI: 10.3390/cells11050811.

References

Chen X, Elsheikha H, Hu R, Hu G, Guo S, Zhou C . Hepatic Metabolomics Investigation in Acute and Chronic Murine Toxoplasmosis. Front Cell Infect Microbiol. 2018; 8:189. PMC: 5996072. DOI: 10.3389/fcimb.2018.00189. View

Ustun S, Aksoy U, Dagci H, Ersoz G . Incidence of toxoplasmosis in patients with cirrhosis. World J Gastroenterol. 2004; 10(3):452-4. PMC: 4724918. DOI: 10.3748/wjg.v10.i3.452. View

Chen X, Zhou C, Elsheikha H, He S, Hu G, Zhu X . Profiling of the perturbed metabolomic state of mouse spleen during acute and chronic toxoplasmosis. Parasit Vectors. 2017; 10(1):339. PMC: 5516376. DOI: 10.1186/s13071-017-2282-6. View

Shahnazari S, Yen W, Birmingham C, Shiu J, Namolovan A, Zheng Y . A diacylglycerol-dependent signaling pathway contributes to regulation of antibacterial autophagy. Cell Host Microbe. 2010; 8(2):137-46. PMC: 3668700. DOI: 10.1016/j.chom.2010.07.002. View

Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez J . pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011; 12:77. PMC: 3068975. DOI: 10.1186/1471-2105-12-77. View

Ingram W, Goodrich L, Robey E, Eisen M . Mice infected with low-virulence strains of Toxoplasma gondii lose their innate aversion to cat urine, even after extensive parasite clearance. PLoS One. 2013; 8(9):e75246. PMC: 3776761. DOI: 10.1371/journal.pone.0075246. View

van den Bosch H . Phosphoglyceride metabolism. Annu Rev Biochem. 1974; 43(0):243-77. DOI: 10.1146/annurev.bi.43.070174.001331. View

Reeber S, Otis T, Sillitoe R . New roles for the cerebellum in health and disease. Front Syst Neurosci. 2013; 7:83. PMC: 3827539. DOI: 10.3389/fnsys.2013.00083. View

Shapira Y, Agmon-Levin N, Renaudineau Y, Porat-Katz B, Barzilai O, Ram M . Serum markers of infections in patients with primary biliary cirrhosis: evidence of infection burden. Exp Mol Pathol. 2012; 93(3):386-90. DOI: 10.1016/j.yexmp.2012.09.012. View

10.

Frankle W, Laruelle M . Neuroreceptor imaging in psychiatric disorders. Ann Nucl Med. 2003; 16(7):437-46. DOI: 10.1007/BF02988639. View

11.

Mendez O, Koshy A . Toxoplasma gondii: Entry, association, and physiological influence on the central nervous system. PLoS Pathog. 2017; 13(7):e1006351. PMC: 5519211. DOI: 10.1371/journal.ppat.1006351. View

12.

Boillat M, Hammoudi P, Dogga S, Pages S, Goubran M, Rodriguez I . Neuroinflammation-Associated Aspecific Manipulation of Mouse Predator Fear by Toxoplasma gondii. Cell Rep. 2020; 30(2):320-334.e6. PMC: 6963786. DOI: 10.1016/j.celrep.2019.12.019. View

13.

Sawin E, Murali S, Ney D . Differential effects of low-phenylalanine protein sources on brain neurotransmitters and behavior in C57Bl/6-Pah(enu2) mice. Mol Genet Metab. 2014; 111(4):452-61. PMC: 3995025. DOI: 10.1016/j.ymgme.2014.01.015. View

14.

Tyebji S, Seizova S, Garnham A, Hannan A, Tonkin C . Impaired social behaviour and molecular mediators of associated neural circuits during chronic Toxoplasma gondii infection in female mice. Brain Behav Immun. 2019; 80:88-108. DOI: 10.1016/j.bbi.2019.02.028. View

15.

Carrasco S, Merida I . Diacylglycerol, when simplicity becomes complex. Trends Biochem Sci. 2006; 32(1):27-36. DOI: 10.1016/j.tibs.2006.11.004. View

16.

Zhou C, Cong W, Chen X, He S, Elsheikha H, Zhu X . Serum Metabolic Profiling of Oocyst-Induced Acute and Chronic Infections in Mice Using Mass-Spectrometry. Front Microbiol. 2018; 8:2612. PMC: 5761440. DOI: 10.3389/fmicb.2017.02612. View

17.

Iannotti F, Di Marzo V, Petrosino S . Endocannabinoids and endocannabinoid-related mediators: Targets, metabolism and role in neurological disorders. Prog Lipid Res. 2016; 62:107-28. DOI: 10.1016/j.plipres.2016.02.002. View

18.

McConkey G, Peers C, Prandovszky E . Reproducing increased dopamine with infection to evaluate the role of parasite-encoded tyrosine hydroxylase activity. Infect Immun. 2015; 83(8):3334-5. PMC: 4496599. DOI: 10.1128/IAI.00605-15. View

19.

Prandovszky E, Gaskell E, Martin H, Dubey J, Webster J, McConkey G . The neurotropic parasite Toxoplasma gondii increases dopamine metabolism. PLoS One. 2011; 6(9):e23866. PMC: 3177840. DOI: 10.1371/journal.pone.0023866. View

20.

Gasper D, Neldner B, Plisch E, Rustom H, Carrow E, Imai H . Effective Respiratory CD8 T-Cell Immunity to Influenza Virus Induced by Intranasal Carbomer-Lecithin-Adjuvanted Non-replicating Vaccines. PLoS Pathog. 2016; 12(12):e1006064. PMC: 5173246. DOI: 10.1371/journal.ppat.1006064. View