Role of the Kynurenine Pathway in Epilepsy

  • Monika Sharma
  • Chaitali Anand
  • Diane C. ChuganiEmail author


A role for the kynurenine pathway (KP) of tryptophan (TRP) metabolism in epilepsy was first discovered when injections of the KP metabolite quinolinic acid (QA) in brain produced seizures in mice (Lapin IP. J Neural Transm. 42(1):37–43;1978). Subsequent studies have reported altered KP metabolites in animal models of epilepsy and in human epilepsy. Epilepsy is a complex group of disorders involving abnormal firing of neurons linked to an imbalance of excitatory and inhibitory mechanisms in the brain. KP metabolites act at several neurotransmitter receptors and can produce both excitatory and inhibitory effects. Thus, the role of the KP mechanisms in epilepsy, a condition characterized by an imbalance in excitation and inhibition, is important to consider. Furthermore, the KP is induced by inflammatory cytokines and is part of the inflammatory response increasingly recognized to play a role in epilepsy and epileptogenesis (Vezzani A. Epilepsy Curr. 14(1 Suppl):3–7;2014). In this chapter, we discuss evidence for the role of the KP in the balance of excitation and inhibition and the inflammatory process in animal models, as well as evidence for a role of kynurenines in human epilepsy. Finally, therapeutic targets for epilepsy in the KP are discussed.


Epilepsy Kynurenine Tryptophan Inflammation α-[11C]methyl-l-tryptophan 

List of Abbreviations




α-Amino-β-carboxymuconate-ε-semialdehyde decarboxylase


α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid




Cerebrospinal fluid


Indoleamine 2,3-dioxygenase (IDO)


Kynurenine aminotransferases


Kynurenine monoxygenase


Kynurenine pathway


Kynurenic acid




New-onset refractory status epilepticus


Positron emission tomography




Quinolinic acid




Tuberous sclerosis complex



This work was supported by the U.S. National Institutes of Health (NINDS 5R01NS064989-03).


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Monika Sharma
    • 1
  • Chaitali Anand
    • 2
  • Diane C. Chugani
    • 1
    • 3
    Email author
  1. 1.Carman and Ann Adams Department of Pediatrics, Children’s Hospital of Michigan, Detroit Medical CenterWayne State University School of MedicineDetroitUSA
  2. 2.Translational Neuroscience Program, Children’s Hospital of Michigan, Detroit Medical CenterWayne State University School of MedicineDetroitUSA
  3. 3.Division of Clinical Pharmacology and Toxicology, Children’s Hospital of MichiganWayne State University School of MedicineDetroitUSA

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