Iron deposition in substantia nigra: abnormal iron metabolism, neuroinflammatory mechanism and clinical relevance

Xi-Yan Huang,Wei Zhang,Li-Jun Zuo,Hui-Cong Shen,Shou-Xian Tang,Chen-Jie Cao,Shu-Yang Yu,Peng Guo,Xiao-Min Wang,Piu Chan,Teng-Hong Lian,Lei Mao,Sheng-Di Chen,Zhuo Liu,Li Sun

doi:10.1038/s41598-017-14721-1

Abstract

Parkinson disease (PD) is associated with multiple factors, including iron, which is demonstrated to deposit excessively in PD brains. We detected iron deposition by susceptibility weighted image (SWI) and measured the levels of iron metabolism-related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum of PD patients and control subjects. Clinical symptoms of PD were evaluated by series of rating scales. Relationships among above factors were analyzed. Results showed that corrected phase (CP) value of substantia nigra (SN) was significantly decreased in PD group compared to control group, hence, SN was the main region with excessive iron deposition. In PD group, ferritin was significantly elevated in CSF and reduced in serum compared to control group, and levels of ferritin in CSF and serum were both significantly and positively correlated with CP value of SN, thus, abnormal iron metabolism in central and peripheral systems was associated with iron deposition. CP value of SN in PD group was significantly and negatively correlated with interleukin-1β level in CSF, so interleukin-1β might be a neuroinflammatory factor produced by excessive iron in SN. Iron deposition in SN was significantly correlated with motor symptoms and part of non-motor symptoms of PD.

Highlights

Parkinson disease (PD) is a common neurodegenerative disorder, which is mainly characterized by motor symptoms, and is often accompanied by an array of non-motor symptoms, such as psychiatric symptoms, sleep disorders, autonomic dysfunctions and abnormal sensation, etc[1]
In PD patients and control subjects recruited in this investigation, iron deposition was detected by susceptibility weighted image (SWI), the levels of iron metabolism-related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum were measured, motor symptoms and non-motor symptoms of PD patients were evaluated by a body of rating scales, and the relationships among the factors above were analyzed eventually
The corrected phase (CP) values of substantia nigra (SN), caudate nucleus, putamen and globus pallidus detected by SWI were 2051.64, 2086.32, 2053.69 and 2041.49, respectively, which were all significantly and negatively correlated with iron level according to the technique set up by Hallgren[9] (r = −0.902, P < 0.05) (Fig. 1)

Summary

Introduction

Parkinson disease (PD) is a common neurodegenerative disorder, which is mainly characterized by motor symptoms, and is often accompanied by an array of non-motor symptoms, such as psychiatric symptoms, sleep disorders, autonomic dysfunctions and abnormal sensation, etc[1]. In PD patients, the relationships between iron deposition in SN, the clinical motor symptoms and non-motor symptoms haven’t been well elucidated. It remains unknown what a role of neuroinflammatory mechanism plays on the relationship between iron deposition in SN and clinical symptoms. In PD patients and control subjects recruited in this investigation, iron deposition was detected by susceptibility weighted image (SWI), the levels of iron metabolism-related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum were measured, motor symptoms and non-motor symptoms of PD patients were evaluated by a body of rating scales, and the relationships among the factors above were analyzed eventually

Methods

Results

Conclusion