Title: Low plasma serotonin linked to higher nigral iron in Parkinson's disease.
Authors: Jellen, Leslie C; Lewis, Mechelle M; Du, Guangwei; Wang, Xi; Galvis, Martha L Escobar; Krzyzanowski, Stanislaw; Capan, Colt D; Snyder, Amanda M; Connor, James R; Kong, Lan; Mailman, Richard B; Brundin, Patrik; Brundin, Lena; Huang, Xuemei
Published In Sci Rep, (2021 12 21)
Abstract: A growing body of evidence suggests nigral iron accumulation plays an important role in the pathophysiology of Parkinson's disease (PD), contributing to dopaminergic neuron loss in the substantia nigra pars compacta (SNc). Converging evidence suggests this accumulation might be related to, or increased by, serotonergic dysfunction, a common, often early feature of the disease. We investigated whether lower plasma serotonin in PD is associated with higher nigral iron. We obtained plasma samples from 97 PD patients and 89 controls and MRI scans from a sub-cohort (62 PD, 70 controls). We measured serotonin concentrations using ultra-high performance liquid chromatography and regional iron content using MRI-based quantitative susceptibility mapping. PD patients had lower plasma serotonin (p < 0.0001) and higher nigral iron content (SNc: p < 0.001) overall. Exclusively in PD, lower plasma serotonin was correlated with higher nigral iron (SNc: r(58) = - 0.501, p < 0.001). This correlation was significant even in patients newly diagnosed (< 1 year) and stronger in the SNc than any other region examined. This study reveals an early, linear association between low serotonin and higher nigral iron in PD patients, which is absent in controls. This is consistent with a serotonin-iron relationship in the disease process, warranting further studies to determine its cause and directionality.
PubMed ID: 34934078
MeSH Terms: Aged; Cohort Studies; Female; Humans; Iron/metabolism*; Magnetic Resonance Imaging; Male; Middle Aged; Parkinson Disease/diagnostic imaging; Parkinson Disease/drug therapy; Parkinson Disease/metabolism*; Serotonin Uptake Inhibitors/pharmacology; Serotonin Uptake Inhibitors/therapeutic use; Serotonin and Noradrenaline Reuptake Inhibitors/metabolism; Serotonin and Noradrenaline Reuptake Inhibitors/pharmacology; Serotonin and Noradrenaline Reuptake Inhibitors/therapeutic use; Serotonin/blood*; Severity of Illness Index; Substantia Nigra/diagnostic imaging; Substantia Nigra/metabolism*; Time