Tryptophan is metabolized into metabolites which have neuroprotective or neurotoxic properties. Alteration of the activity of enzymes which mediate tryptophan metabolism pathway is known in various neurological disorders. We investigated tryptophan metabolite level and enzyme activity in mouse groups with different age, and in groups administrated with voluntary chronic aerobic exercise by wheel running. Focal cerebral ischemia model induced by middle cerebral artery occlusion were used to see changes in acute and chronic cerebral ischemia. For human study, serum tryptophan metabolite level and enzyme activity were measured from 55 ischemic stroke patients and 28 control subjects. Demographic data, clinical data and brain MRI findings were retrospectively reviewed. In the animal study, serum kynurenic acid level, kynurenine aminotransferase (KAT) activity, and KAT/kynurenine 3 monooxygenase (KMO) ratio decreased according to age. Exercise group showed higher KAT activity, KAT/KMO ratio and lower KMO activity in some age groups. In cerebral ischemia model, indoleamine 2,3-dioxygenase (IDO) activity and KMO activity increased in acute stage, while KAT activity and KAT/KMO ratio decreased. In the human study KAT and KMO activity decreased according to age. Ischemic stroke patients showed higher IDO activity. Higher IDO activity, lower KAT activity, and KAT/KMO ratio were associated with poor functional outcome. Tryptophan metabolites and enzyme activity alter according to aging, exercise and cerebral infarction. They are a possible marker for aging and ischemic stroke, and future study might reveal their role in disease mechanism and moreover might be a potential target for intervention.
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Alteration of tryptophan metabolites and enzyme activity in aging, exercise and ischemic stroke: study in mouse and human
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