Kazuhiro Iwaoka1, Chigumi Otsuka2, Tetsuya Maeda3, Kanako Yamahara4, Kanako Kato5, Kenta Takahashi6, Kai Takahashi7, Yasuo Terayama8. 1. Division of Neurology and Gerontology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan. Electronic address: kiwaoka@iwate-med.ac.jp. 2. Division of Neurology and Gerontology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan. Electronic address: chigohtsuka@gmail.com. 3. Division of Neurology and Gerontology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan. Electronic address: maeda@iwate-med.ac.jp. 4. Division of Neurology and Gerontology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan. Electronic address: kkonno@iwate-med.ac.jp. 5. Division of Neurology and Gerontology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan. Electronic address: kanakana117421@yahoo.co.jp. 6. Division of Neurology and Gerontology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan. Electronic address: ktakahashi1009@gmail.com. 7. Division of Neurology and Gerontology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan. Electronic address: sea.t.0926@gmail.com. 8. Division of Neurology and Gerontology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan. Electronic address: surabe@iwate-med.ac.jp.
Abstract
AIM: The kynurenine (KYN) pathway plays an important role in degrading molecules responsible for oxidative stress in the central nervous system (CNS), but can also have neurotoxic effects. Both 3-hydroxykynurenine (3-HK) and quinolinic acid are neurotoxic metabolites produced from this pathway. In Parkinson's disease (PD), oxidative stress is suspected to represent a key pathogenic mechanism. This study aimed to investigate the function of the KYN pathway and interactions between oxidative stress and neuroinflammation in PD. METHODS: Participants comprised 20 patients with PD and 13 controls. Cerebrospinal fluid (CSF) levels of KYN and 3-HK were measured using high-performance liquid chromatography coupled with an electrochemical detector. CSF levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and interferon (IFN)-γ were measured with an enzyme-linked immunosorbent assay, and results were statistically compared between PD patients and controls. RESULTS: Median CSF levels of KYN and 3-HK were 49.0 nM and 4.25 nM in PD and 30.5 nM and 1.55 nM in controls, respectively, showing significantly higher levels in PD (p < 0.05). CSF levels of measured cytokines showed that TNF-α and IL-1β were significantly higher in PD patients than in controls. No positive correlation between 3-HK and TNF-α was seen in PD. CONCLUSION: Dysfunction of the KYN pathway may induce oxidative stress in the CNS in PD, and may also induce cytokine-mediated neuroinflammation. Functional amelioration of the KYN pathway may facilitate modification of neurodegenerative processes in PD.
AIM: The kynurenine (KYN) pathway plays an important role in degrading molecules responsible for oxidative stress in the central nervous system (CNS), but can also have neurotoxic effects. Both 3-hydroxykynurenine (3-HK) and quinolinic acid are neurotoxic metabolites produced from this pathway. In Parkinson's disease (PD), oxidative stress is suspected to represent a key pathogenic mechanism. This study aimed to investigate the function of the KYN pathway and interactions between oxidative stress and neuroinflammation in PD. METHODS:Participants comprised 20 patients with PD and 13 controls. Cerebrospinal fluid (CSF) levels of KYN and 3-HK were measured using high-performance liquid chromatography coupled with an electrochemical detector. CSF levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and interferon (IFN)-γ were measured with an enzyme-linked immunosorbent assay, and results were statistically compared between PDpatients and controls. RESULTS: Median CSF levels of KYN and 3-HK were 49.0 nM and 4.25 nM in PD and 30.5 nM and 1.55 nM in controls, respectively, showing significantly higher levels in PD (p < 0.05). CSF levels of measured cytokines showed that TNF-α and IL-1β were significantly higher in PDpatients than in controls. No positive correlation between 3-HK and TNF-α was seen in PD. CONCLUSION: Dysfunction of the KYN pathway may induce oxidative stress in the CNS in PD, and may also induce cytokine-mediated neuroinflammation. Functional amelioration of the KYN pathway may facilitate modification of neurodegenerative processes in PD.
Authors: Michael Y Bai; David B Lovejoy; Gilles J Guillemin; Rouba Kozak; Trevor W Stone; Maju Mathew Koola Journal: Complex Psychiatry Date: 2021-02-08
Authors: Elisabeth R Paul; Lilly Schwieler; Sophie Erhardt; Sandra Boda; Ada Trepci; Robin Kämpe; Anna Asratian; Lovisa Holm; Adam Yngve; Robert Dantzer; Markus Heilig; J Paul Hamilton; Martin Samuelsson Journal: Brain Behav Immun Date: 2022-01-06 Impact factor: 19.227