Analysis Tools
behavior/neurological
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• mice display anxiety-like behavior, showing reduced distance traveled, reduced distance in the center and much less time spend in the center of the open-field test
• however, mice exhibit normal extinction of fear memory in the continuous elevated plus-maze test
• treatment with BCX-1777, a purine nucleoside phosphorylase inhibitor, reduces anxiety symptoms
• mice treated with an adeno-associated virus expressing myelin basic protein promoter-driven Adora1 shRNA to knock-down the adenosine receptor A1 in oligodendrocytes rescues the anxiety phenotype
• treatment with 2-Deoxy-D-glucose, a glucose analog that inhibits its catabolic pathways, normalizes the anxiety-like symptoms
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• mice spend much less time in the center of the open-field test
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hematopoietic system
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• CD4+ T cells exhibit reduced activities of oxidative phosphorylation and glycolysis
• naive CD4+ T cells have lower glycolysis but produce more M+5 ribulose-5-p, CAIR, adenosine, and inosine
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homeostasis/metabolism
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• various amino acids are upregulated in the serum, with highest increases in methionine, threonine, arginine, alanine, and proline
• however, levels of 5-HTP, serotonin, glutamate, and GABA are not affected
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• metabolites involved in purine metabolism are enriched in the serum, with most of the purines and their derivatives including adenine, hypoxanthine, and xanthine 10-100 times more abundant
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• xanthine levels are 10-100 times more abundant in serum
• treatment with BCX-1777 reduces serum xanthine levels
• depletion of CD4+ T cells with an anti-CD4 antibody decreases serum xanthine level
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immune system
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• T cells do not show any obvious abnormalities in the development and homeostasis of T lymphocytes and mice show comparable sensitivities in models of experimental autoimmune encephalomyelitis as controls
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• CD4+ T cells exhibit reduced activities of oxidative phosphorylation and glycolysis
• naive CD4+ T cells have lower glycolysis but produce more M+5 ribulose-5-p, CAIR, adenosine, and inosine
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• xanthine levels are decreased in the peripheral immune organs
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nervous system
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• xanthine accumulates in the brain
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• left amygdala exhibits higher numbers of nonneuronal cells than the right amygdala or wild-type left amygdala
• amygdala shows an increase in the percentage of oligodendrocytes
• treatment with 2-Deoxy-D-glucose normalizes the pathological changes of the left amygdala
• depletion of CD4+ T cells with an anti-CD4 antibody decreases the oligodendrocyte percentage in the amygdala
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• left amygdala is enlarged
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