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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.

SUBMITTER: Jellen LC

PROVIDER: S-EPMC8692322 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Serum uric acid and nigral iron deposition in Parkinson's disease: a pilot study.

Project description:BackgroundUric acid (UA) is an endogenous antioxidant which is known to reduce oxidative stress and also chelate iron ion. Recent studies have provided evidence that UA may play a neuroprotective role in Parkinson's disease (PD). However, it is unknown whether UA relates to nigral iron deposition, which is a characteristic pathophysiological alteration in PD. The aim of this study was to determine the potential relationship of these two markers in patients with PD.MethodsA total of 30 patients of PD and 25 age- and gender- matched healthy controls underwent 3-Tesla MRI and laboratory tests including serum UA levels. We assessed iron levels by measuring phase shift values using susceptibility-weighted image. Mean phase shift values of the substantia nigra (SN), red nucleus, head of the caudate nucleus, globus pallidus, putamen, thalamus, and frontal white matter were calculated and correlated with serum UA levels.ResultsSerum UA levels were significantly decreased in the PD patients than in the controls. Phase shift values in bilateral SN were significantly increased in the PD patients than in the controls. There was no significant correlation between serum UA levels and nigral phase shift values.ConclusionsAs previous studies, low serum UA level and increased nigral iron content in the PD was reconfirmed in this study. However, we failed to find the relationship between these two markers. Our data suggest that serum UA may not be important determinant of nigral iron deposition in PD.

| S-EPMC4227693 | biostudies-literature

Project description:In Parkinson's disease (PD), iron accumulation in the substantia nigra (SN) exacerbates oxidative stress and α-synuclein aggregation, leading to neuronal death. However, the influence of iron-related nigral degeneration on the subcortical function and global network configuration in PD remains unknown. Ninety PD patients and 38 normal controls underwent clinical assessments and multimodality magnetic resonance imaging scans. Iron accumulation in the inferior SN and disrupted functional connectivity between the bilateral striatums were observed in PD, and negative correlation between them was found in the whole population. The binarized functional network exhibited enhanced global efficiency and reduced local efficiency while the weighted functional network exhibited reduction in both, and both changes were correlated with nigral iron accumulation in PD. Mediation analysis demonstrated that the functional connectivity between bilateral striatums was a mediator between the nigral iron accumulation and weighted functional network alterations. In conclusion, our findings reveal that iron-related nigral degeneration possibly influences the functional topology mediated by striatal dysfunction, which extends the scientific understanding of PD pathogenesis.

| S-EPMC6538269 | biostudies-literature

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Imaging nigral pathology and clinical progression in Parkinson's disease.

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Differential involvement of nigral subregions in idiopathic parkinson's disease.

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| S-EPMC7806895 | biostudies-literature

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Project description:Dopamine cell loss and increased iron in the substantia nigra (SN) characterize Parkinson's disease (PD), with cerebellar involvement increasingly recognized, particularly in motor compensation and levodopa-induced dyskinesia (LID) development. Because the red nucleus (RN) mediates cerebellar circuitry, we hypothesized that RN iron changes might reflect cerebellum-related compensation, and/or the intrinsic capacity for LID development. We acquired high resolution magnetic resonance images from 23 control and 38 PD subjects (12 with PD and history of LID [PD+DYS]) and 26 with PD and no history of LID (PD-DYS). Iron content was estimated from bilateral RN and SN transverse relaxation rates (R2*). PD subjects overall displayed higher R2* values in both the SN and RN. RN R2* values correlated with off-drug Unified Parkinson's Disease Rating Scale-motor scores, but not disease duration or drug dosage. RN R2* values were significantly higher in PD+DYS compared with control and PD-DYS subjects; control and PD-DYS subjects did not differ. The association of higher RN iron content with PD-related dyskinesia suggests increased iron content is involved in, or reflects, greater cerebellar compensatory capacity and thus increased likelihood of LID development.

| S-EPMC3570638 | biostudies-literature

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