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The Effect of Kynurenine Pathway on cognitive Function

(2019) Almatrood, R. (Rajaie)

Kynurenine pathway began to get more attention over the years for its role in neurodegenerative diseases and psychiatric disorders. The kynurenine pathway is seen as the link between the immune system and the brain. Activation of the kynurenine pathway and high levels of its metabolites are thought to worsen the cognitive function in schizophrenia and depression through the action of kynurenic acid (KYNA) and quinolinic acid (QUIN), respectively. Furthermore, QUIN was seen to contribute to the damage seen in Alzheimer’s disease through generation of free radicals and reactive oxygen species. Moreover, QUIN can lead to damage of the blood brain barrier, which then can lead to infiltration of harmful substance to the brain. KYNA is thought to contribute to cognitive impairment through its action on N-methyl-D-aspartate receptors (NMDARs) and subsequent changes of glutamate level.
The kynurenine pathway was mostly studied in pathological studies. To our knowledge, there are no studies that extensively evaluated the effect of the kynurenine metabolites on cognition in relatively neurologically healthy people. We investigated the effect of the kynurenine pathway on cognitive function in this study of 61 neurologically healthy patients undergoing elective surgery and getting spinal anesthesia.
It was found that kynurenine metabolites contribute to cognitive dysfunction in these patients as well. Kynurenic acid and quinolinic acid were both found to worsen cognitive function in our study. The presence of high level of tryptophan, the precursor of the kynurenine pathway, was seen to be protective of cognitive function. Our conclusion is that kynurenine pathway contributes to cognitive dysfunction even in the absence of neurological disease or psychiatric disorder.

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