CORRELATING RATIOS OF AMINES IN PLASMA AND CEREBROSPINAL FLUID 67 3 related to the synthesis of neurotransmitters, such as glutamine and glutathione for glutamic acid and GABA and tryptophan for serotonin,9 also did not show strong correlation between plasma and CSF.Thus, plasma levels of these metabolites seem not be useful to infer or predict CSF levels. In our interictal migraine group, significant changes of six amine (which were mainly amino acids) related ratios were observed when comparing the plasma/CSF R2 ratios of participants with migraine to those of healthy controls. The most likely explanation for this finding would be an underlying malfunctioning of the respective amine cotransporter in migraine, resulting in a difference between R2 ratios of patients and healthy volunteers. Most of the changed ratios are related to the L1 transporter system. It has previously been demonstrated that the ratio between amino acids is important for the entry to the brain and that there is competition between these NAAs for the entry into the brain.30 In addition, the L-Arginine/S-Methylcysteine ratio was increased in migraine participants, while these amines are not transported by the L1 system. Arginine is transported by the y+ or the cationic amino acid (CAA) transport (CAT) system.24, 26 The CAT system is primarily a CAA transporter, but also exhibits weak interactions with NAAs (phenylalanine, threonine, histidine, valine, methionine, serine, glutamine, alanine, and glycine).24, 31 Arginine levels in CSF were previously found to be associated with migraine by our group 13. Of note, arginine forms a caveolar complex with endothelial nitric oxide synthase (eNOS) to form nitric oxide (NO) 32. Interestingly, NO has previously been implicated in migraine pathophysiology 33-35. Although the current study does not allow for a detailed analysis of the mentioned transport mechanisms, the ratios can still be useful for assessing CNS metabolism of amines. For example, if a person has a high leucine/methionine ratio in plasma, this is likely also the case in CSF. If this plasma ratio changes over time within this person, due to a certain disease process, one can envisage that the CSF ratio may also change. Of course, this must be proven in a longitudinal design with additional evidence that there is indeed a relationship between the specific ratio and the disease process. The strengths of this study are the large number of participants and the wide coverage of amine molecules measured. There are also some limitations. We did not have repeated measurements for individual participants and could not validate our findings for dynamic changes. Hence, future (dynamic) studies should replicate the identified correlations. In conclusion, for individual amine metabolites there is generally poor correlation between the concentrations in plasma and CSF. However, ratios of certain amines show a good correlation of plasma with CSF. Plasma amine measurements thus have the potential to be used for predicting CSF metabolite levels, which can be very relevant to assess fluctuations of amino acids and biogenic amines metabolism in paroxysmal CNS disorders.
RkJQdWJsaXNoZXIy MTk4NDMw