@article{cfb2ccefa3d34279bb0de14a58632ed3,
title = "Low plasma serotonin linked to higher nigral iron in Parkinson{\textquoteright}s disease",
abstract = "A growing body of evidence suggests nigral iron accumulation plays an important role in the pathophysiology of Parkinson{\textquoteright}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.",
author = "Jellen, {Leslie C.} and Lewis, {Mechelle M.} and Guangwei Du and Xi Wang and Galvis, {Martha L.Escobar} and Stanislaw Krzyzanowski and Capan, {Colt D.} and Snyder, {Amanda M.} and Connor, {James R.} and Lan Kong and Mailman, {Richard B.} and Patrik Brundin and Lena Brundin and Xuemei Huang",
note = "Funding Information: Dr. Huang and Dr. Lewis have received funding from the National Institutes of Health (R01 ES019672, U01 NS082151, U01 NS112008), the Michael J. Fox Foundation, Alzheimer{\textquoteright}s Association, Alzheimer{\textquoteright}s Research UK, the Weston Brain Institute, Bristol Myers Squibb/Biogen, Pfizer, and the Department of Defense. Dr. Huang and Dr. Lewis also have a patent covering the use of novel imaging metrics to diagnose PD and monitor its progression. Dr. Du received funding from the National Institutes of Health (R01 ES019672, U01 NS082151, U01 NS112008), the Michael J. Fox Foundation for Parkinson{\textquoteright}s Research, Alzheimer{\textquoteright}s Association, Alzheimer{\textquoteright}s Research UK, and the Weston Brain Institute. Dr. Du also has a patent covering the use of novel imaging metrics to diagnose PD and monitor its progression. Dr. Kong received funding from NINDS, NIEHS, NCATS, the Patient-Centered Outcomes Research Institute (PCORI), the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR), the National Institute of Aging (NIA), and Pfizer. Dr. Lena Brundin has received funding from the National Institute of Mental Health, the United States Department of Veterans Affairs and the Michael J Fox Foundation for Parkinson{\textquoteright}s Research. Dr. Patrik Brundin has consulted for Axial Therapeutics, Calico, CuraSen, Fujifilm-Cellular Dynamics Inc, Idorsia and Lundbeck A/S. He has received commercial support for research from Lundbeck A/S and Roche, and has ownership interests in Acousort AB. The rest of the authors declare to have no competing interest. Funding Information: We express gratitude to all of the participants who volunteered for this study and study personnel who contributed to its success. We also would like to acknowledge the RTSF Mass Spectrometry and Metabolomics Core at Michigan State University for their help in measuring serotonin. All analyses, interpretations, and conclusions are those of the authors and not the research sponsors. This work was supported in part by the Michael J Fox Foundation for Parkinson{\textquoteright}s Research (Grant 14939), National Institute of Neurological Disorders and Stroke Parkinson{\textquoteright}s Disease Biomarker Program (NS082151 and NS112008 to XH), the Hershey Medical Center General Clinical Research Center (National Center for Research Resources, Grant UL1 RR033184 that is now at the National Center for Advancing Translational Sciences, Grant UL1 TR000127), the PA Department of Health Tobacco CURE Funds, and the Penn State Translational Brain Research Center. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1038/s41598-021-03700-2",
language = "English (US)",
volume = "11",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}