Hoosierfans
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From the recent article out of Ohio State: https://www.mdpi.com/2218-273X/11/2/185/htm
“Finally, these studies found that the EBV dUTPase protein modulates tryptophan, serotonin, and dopamine metabolism and use in vitro and in vivo. The EBV dUTPase may alter kynurenine catabolism in microglia in vitro by increasing the expression of indoleamine 2,3 dioxygenase (IDO1) and kynurenine-3-monooxygenase (KMO), suggesting that there is an increase synthesis of quinolinic acid. Quinolinic acid, an agonist of NMDAR, can cause overstimulation that results in neuronal toxicity. Furthermore, the data suggest the EBV dUTPase protein increases the expression of GTP cyclohydrolase (Gch1), and down-regulates both tryptophan hydrolase 2 (Tph2) and tyrosine hydrolase (Th). Gch1 is the rate limiting enzyme necessary for the synthesis of tetrahydropterin (BH4), a substrate required for serotonin and dopamine synthesis by Tph2 and Th, respectively. Furthermore, the dopamine receptors Drd1 and Drd5, as well as the serotonin transporter gene Slc6a4, were also down-regulated. These results suggest that the decreased synthesis and recycling of dopamine and serotonin coupled with the increased degradation by astrocytes and microglia could result in low levels of these neurotransmitters ultimately leading to cognitive defects and increased oxidative stress. The dopaminergic and serotonergic neurotransmitter systems are reported to play a critical role in the regulation of emotion and mood, and have been implicated in a wide spectrum of neuropsychiatric disorders. Specifically, EBV dUTPase simultaneously down-regulated key genes involved with dopamine and serotonin synthesis as well as key transporters and receptors required for signaling by these molecules. Low dopamine levels are associated with fatigue, attention deficits, decreased motivation and depression [122], while low serotonin levels are associated with fatigue, cognitive impairments, anxiety and digestive problems [123]. These are common symptoms associated with ME/CFS. Morris et al. [124,125] proposed that alterations in tryptophan catabolism may contribute to a variety of symptoms observed in several neuroimmune disorders including ME/CFS.”
“Finally, these studies found that the EBV dUTPase protein modulates tryptophan, serotonin, and dopamine metabolism and use in vitro and in vivo. The EBV dUTPase may alter kynurenine catabolism in microglia in vitro by increasing the expression of indoleamine 2,3 dioxygenase (IDO1) and kynurenine-3-monooxygenase (KMO), suggesting that there is an increase synthesis of quinolinic acid. Quinolinic acid, an agonist of NMDAR, can cause overstimulation that results in neuronal toxicity. Furthermore, the data suggest the EBV dUTPase protein increases the expression of GTP cyclohydrolase (Gch1), and down-regulates both tryptophan hydrolase 2 (Tph2) and tyrosine hydrolase (Th). Gch1 is the rate limiting enzyme necessary for the synthesis of tetrahydropterin (BH4), a substrate required for serotonin and dopamine synthesis by Tph2 and Th, respectively. Furthermore, the dopamine receptors Drd1 and Drd5, as well as the serotonin transporter gene Slc6a4, were also down-regulated. These results suggest that the decreased synthesis and recycling of dopamine and serotonin coupled with the increased degradation by astrocytes and microglia could result in low levels of these neurotransmitters ultimately leading to cognitive defects and increased oxidative stress. The dopaminergic and serotonergic neurotransmitter systems are reported to play a critical role in the regulation of emotion and mood, and have been implicated in a wide spectrum of neuropsychiatric disorders. Specifically, EBV dUTPase simultaneously down-regulated key genes involved with dopamine and serotonin synthesis as well as key transporters and receptors required for signaling by these molecules. Low dopamine levels are associated with fatigue, attention deficits, decreased motivation and depression [122], while low serotonin levels are associated with fatigue, cognitive impairments, anxiety and digestive problems [123]. These are common symptoms associated with ME/CFS. Morris et al. [124,125] proposed that alterations in tryptophan catabolism may contribute to a variety of symptoms observed in several neuroimmune disorders including ME/CFS.”
