Neurotransmitter imbalance, glutathione depletion and concomitant susceptibility increase in Parkinson’s disease

IF 3.4 2区医学 Q2 NEUROIMAGING

Neuroimage-Clinical Pub Date : 2025-01-01 DOI:10.1016/j.nicl.2025.103740

Su Yan , Bingfang Duan , Yuanhao Li , Hongquan Zhu , Zhaoqi Shi , Xiaoxiao Zhang , Yuanyuan Qin , Wenzhen Zhu

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引用次数: 0

Abstract

Background

Emerging insights into the pathophysiology of Parkinson’s disease (PD) underscore the involvement of dysregulated neurotransmission, iron accumulation and oxidative stress. Nonetheless, the excitatory and inhibitory neurometabolites, the antioxidant glutathione (GSH), and magnetic susceptibility are seldom studied together in the clinical PD literature.

Methods

We acquired MEGA-PRESS and multi-echo gradient echo sequences from 60 PD patients and 47 healthy controls (HCs). Magnetic resonance spectroscopy voxels were respectively positioned in the midbrain to quantify neurotransmitter including γ-aminobutyric acid (GABA) and glutamate plus glutamine, and in the left striatum to estimate GSH levels. Group differences in metabolite levels normalized to total creatine (Cr) and their clinical relevance were determined. Furthermore, relationships among GSH levels, neurotransmitter estimates and susceptibility values were explored in both PD patients and HCs.

Results

PD patients exhibited reduced midbrain GABA levels (P = 0.034, P_FDR = 0.136), diminished GSH in the left striatum (P = 0.032, P_FDR = 0.096), and increased susceptibility values in the substantia nigra (P_FDR < 0.001). Mesencephalic choline levels were correlated with the severity of rapid eye movement sleep behavior disorders symptoms, whereas striatal N-acetylaspartate levels were linked to Hoehn-Yahr stage and motor symptom severity. Notably, the disruption of associations between striatal GSH levels and susceptibility values in globus pallidus, as well as midbrain GABA levels, were evident in PD.

Conclusions

These findings offer compelling evidence for metabolic dysregulation in PD, characterized by a concomitant reduction in GABA and GSH levels, alongside iron deposition.

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帕金森病的神经递质失衡、谷胱甘肽耗竭及伴随的易感性增加

背景：对帕金森病（PD）病理生理学的新见解强调了神经传递失调、铁积累和氧化应激的参与。然而，在临床PD文献中，兴奋性和抑制性神经代谢物、抗氧化剂谷胱甘肽（GSH）和磁化率很少被一起研究。方法：获取60例PD患者和47例健康对照（hc）的MEGA-PRESS和多回声梯度回声序列。磁共振波谱体素分别位于中脑，用于定量γ-氨基丁酸（GABA）和谷氨酸+谷氨酰胺等神经递质；位于左纹状体，用于估计GSH水平。以总肌酸（Cr）为标准的代谢物水平的组间差异及其临床相关性被确定。此外，我们还探讨了PD患者和hc患者GSH水平、神经递质估计值和易感性值之间的关系。结果：PD患者中脑GABA水平降低（P = 0.034, PFDR = 0.136），左侧纹状体GSH减少（P = 0.032, PFDR = 0.096），黑质易感性值增加（PFDR < 0.001）。中脑胆碱水平与快速眼动睡眠行为障碍症状的严重程度相关，而纹状体n-乙酰天冬氨酸水平与Hoehn-Yahr期和运动症状的严重程度相关。值得注意的是，纹状体GSH水平与苍白球易感性值以及中脑GABA水平之间的关联在PD中明显被破坏。结论：这些发现为PD的代谢失调提供了令人信服的证据，其特征是伴随GABA和GSH水平的降低，以及铁沉积。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroimage-Clinical NEUROIMAGING-

CiteScore

7.50

自引率

4.80%

发文量

368

审稿时长

52 days

期刊介绍： NeuroImage: Clinical, a journal of diseases, disorders and syndromes involving the Nervous System, provides a vehicle for communicating important advances in the study of abnormal structure-function relationships of the human nervous system based on imaging. The focus of NeuroImage: Clinical is on defining changes to the brain associated with primary neurologic and psychiatric diseases and disorders of the nervous system as well as behavioral syndromes and developmental conditions. The main criterion for judging papers is the extent of scientific advancement in the understanding of the pathophysiologic mechanisms of diseases and disorders, in identification of functional models that link clinical signs and symptoms with brain function and in the creation of image based tools applicable to a broad range of clinical needs including diagnosis, monitoring and tracking of illness, predicting therapeutic response and development of new treatments. Papers dealing with structure and function in animal models will also be considered if they reveal mechanisms that can be readily translated to human conditions.