Impacts of CSF kynurenine pathway on neuroinflammaion in patients with Parkinson’s disease
Objective: To investigate the interaction between the KYN pathway and the neuroinflammation in PD. Background: In Parkinson's disease (PD), some pathologic mechanisms are reported such as mitochondrial dysfunction, inflammatory reaction and oxidative stress. Inflammatory cytokines are noticed as one of an important mediator of inflammatory reaction in the central nervous system (CNS). Kynurenine (KYN) pathway is also known to play an important role for degradation of oxidative stress in the CNS. Disproportion of KYN pathway can act neurotoxically and induce several neurological diseases including PD. In metabolites produced from this pathway, 3-hydroxykynurenine (3-HK) and quinolinic acid are as neurotoxic and kynurenic acid (KYNA) is neuroprotective. Methods: We could recruited 20 patients with PD (age; 57-80 y, median; 69.5 y) and 13 controls (age; 23-83 y, median; 75.0 y). Clinical severity was evaluated with Hoehn and Yahr staging.Samples of the cerebrospinal fluid (CSF) were obtained between 9:00 and 10:00AM after overnight bed-rest and before breakfast in PD patients. Control CSF were corrected from normal pregnant women on their lumbar anesthesia ante partum who had no neurologically abnormal condition confirmed by neurological examination and neuroimagings in advance. All CSF samples were promptly cryopreserved in a deep freezer (-80 ℃).CSF levels of KYN or 3-HK were measured using with the high-performance liquid chromatography coupled with the electrochemical detector. CSF levels of IL-6, IL-1β, TNF-α and IFN-γ were also measures using with an ELISA. Statistical analysis was performed and the significance level was set at p<0.05.This study was carried out after approval in our university ethical review board and written informed consents from all participants. Results: CSF levels of KYN in PD and control were 22.6 to 90.3 nM (median; 49.0 nM) and 9.5 to 51.4 nM (30.5 nM), respectively. CFS levels of 3-HK were 0.2 to 13.3 nM (4.25 nM) and 0.001 to 3.96 nM (1.55 nM), respectively. These were significantly higher in PD than in control (p<0.05). These were still statistically significant after normalization to CSF levels of triptophan（p<0.05).There was a positive correlation between the CSF levels of 3-HK and TNF-α (r=0.54,p=0.055). Conclusions: We could suggest that elevated CSF levels of KYN and 3-HK and positive correlation between 3-HK and TNF-α in patients with PD is associated with neuroinflammation in the CNS.Anti-synuclein alpha antibodies and IL-1β at Parkinson Disease (PD).
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Abstracts from the International Congress of Parkinson’s and Movement Disorders.