Low plasma serotonin linked to higher nigral iron in Parkinson’s disease

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.

Brain Iron Homeostasis and Mental Disorders

“…However, alterations in serotonin signaling may also be responsible for emotional behaviors since the neurotransmitter has an important role in mediating affective behaviors. A study in patients with Parkinson's disease (PD) revealed an early, linear association between low serotonin and higher nigral iron, which was absent in controls, warranting further studies to investigate the relationship between brain iron status and serotonin-related emotional behaviors in the pathology of PD [168]. In animal studies, differing results have been observed.…”

Gastrointestinal microbiome and cholelithiasis: Prospect in the nervous system

“…Bearing in mind other studies with neurotransmitters involved in brain impairments GABA and serotonin. For example in the brain GABA in schizophrenic patients (modeling in brain areas by Ferrarelli and Tononi[ 3 ]; auditory cognitive properties by Mugruza-Vassallo and Potter[ 4 ]) as well as the linear association reported for the greater serotonin the lower nigral iron in Parkinson’s disease patients (Jellen et al [ 5 ]).…”

Genetically predicted circulating levels of glycine, glutamate, and serotonin in relation to the risks of three major neurodegenerative diseases: A Mendelian randomization analysis

“…The diagnostic utility of blood glycine and serotonin levels for AD has also been disputed ( Pena-Bautista et al, 2020 ; Gallo et al, 2021 ; Nuzzo et al, 2021 ; Whiley et al, 2021 ). Likewise, it has yet to be determined whether serum neurotransmitters can serve as promising diagnostic biomarkers and potential therapeutic targets of PD ( Tong et al, 2015 ; Jimenez-Jimenez et al, 2020 ; Molsberry et al, 2020 ; Jellen et al, 2021 ; Wichit et al, 2021 ) and ALS ( Andreadou et al, 2008 ; Dupuis et al, 2010 ; Cieslarova et al, 2017 ; Blasco et al, 2018 ; Jia et al, 2021 ). Evidence from these observational studies was compromised due to reverse causation, restricted sample size and confounding factors.…”