Higher iron in the red nucleus marks Parkinson's dyskinesia

Lewis, Mechelle M.; Du, Guangwei; Kidacki, Michal; Patel, Nisargkumar; Shaffer, Michele L.; Mailman, Richard B.; Huang, Xuemei

doi:10.1016/j.neurobiolaging.2012.10.025

Cited by 78 publications

(79 citation statements)

References 45 publications

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“…It has been suggested to be the backup to the corticospinal tract through the connections with the dentate nucleus, the motor cortices and the spinal cord (Nioche et al, 2009, Gruber and Gould, 2010). There also have been studies suggesting that RN increases its function to fulfill cerebellar compensation in the presence of basal ganglia dysfunction (Lewis et al, 2013). Although increased magnetic susceptibility in the RN did exhibit a significant relation to decreased manual dexterity, the RN-manual dexterity relation was not statistically independent of the stronger behavioral correlation exhibited by the GP.…”

Section: Discussionmentioning

confidence: 99%

Association between increased magnetic susceptibility of deep gray matter nuclei and decreased motor function in healthy adults

Langkammer

Chou

et al. 2015

NeuroImage

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In the human brain, iron is more prevalent in gray matter than in white matter, and deep gray matter structures, particularly the globus pallidus, putamen, caudate nucleus, substantia nigra, red nucleus, and dentate nucleus, exhibit especially high iron content. Abnormally elevated iron levels have been found in various neurodegenerative diseases. Additionally, iron overload and related neurodegeneration may also occur during aging, but the functional consequences are not clear. In this study, we explored the correlation between magnetic susceptibility – a surrogate marker of brain iron – of these gray matter structures with behavioral measures of motor and cognitive ability, in 132 healthy adults aged 40–83 years. Latent variables corresponding to manual dexterity and executive functions were obtained using factor analysis. The factor scores for manual dexterity declined significantly with increasing age. Independent of gender, age, and global cognitive function, increasing magnetic susceptibility in the globus pallidus and red nuclei was associated with decreasing manual dexterity. This finding suggests the potential value of magnetic susceptibility, a non-invasive quantitative imaging marker of iron, for the study of iron-related brain function changes.

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Section: Discussionmentioning

confidence: 99%

Association between increased magnetic susceptibility of deep gray matter nuclei and decreased motor function in healthy adults

Langkammer

Chou

et al. 2015

NeuroImage

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“…There is circumstantial evidence of increased cerebellar compensation in LID, as suggested by finding of increased metabolic activity in the deep cerebellar nuclei (Brusa et al 2012) and in the red nucleus (Lewis et al 2013), which is an important projection target of the deep cerebellar nuclei.…”

Section: Role Of the Cerebellummentioning

confidence: 99%

On the neuronal circuitry mediating l-DOPA-induced dyskinesia

2018

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With the advent of rodent models of l-DOPA-induced dyskinesia (LID), a growing literature has linked molecular changes in the striatum to the development and expression of abnormal involuntary movements. Changes in information processing at the striatal level are assumed to impact on the activity of downstream basal ganglia nuclei, which in turn influence brain-wide networks, but very little is actually known about systems-level mechanisms of dyskinesia. As an aid to approach this topic, we here review the anatomical and physiological organisation of cortico-basal ganglia-thalamocortical circuits, and the changes affecting these circuits in animal models of parkinsonism and LID. We then review recent findings indicating that an abnormal cerebellar compensation plays a causal role in LID, and that structures outside of the classical motor circuits are implicated too. In summarizing the available data, we also propose hypotheses and identify important knowledge gaps worthy of further investigation. In addition to informing novel therapeutic approaches, the study of LID can provide new clues about the interplay between different brain circuits in the control of movement.

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“…The substantia nigra, where the selective loss of dopaminergic neurons occurs, is the primary region in the brain known to deposit iron. Additionally, aberrant iron concentrations have been observed in other brain regions such as red nuclei, globus pallidus and cortex of PD patients, despite of unknown pathology123. Spectroscopic analyses of postmortem brains display an increased iron levels in the substantia nigra, which has been suggested to correlate with the severity of PD24.…”

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confidence: 99%

Meta-analysis of brain iron levels of Parkinson’s disease patients determined by postmortem and MRI measurements

Wang

Zhuang

Zhu

et al. 2016

Sci Rep

177

124

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Brain iron levels in patients of Parkinson’s disease (PD) are usually measured in postmortem samples or by MRI imaging including R2* and SWI. In this study we performed a meta-analysis to understand PD-associated iron changes in various brain regions, and to evaluate the accuracy of MRI detections comparing with postmortem results. Databases including Medline, Web of Science, CENTRAL and Embase were searched up to 19th November 2015. Ten brain regions were identified for analysis based on data extracted from thirty-three-articles. An increase in iron levels in substantia nigra of PD patients by postmortem, R2* or SWI measurements was observed. The postmortem and SWI measurements also suggested significant iron accumulation in putamen. Increased iron deposition was found in red nucleus as determined by both R2* and SWI, whereas no data were available in postmortem samples. Based on SWI, iron levels were increased significantly in the nucleus caudatus and globus pallidus. Of note, the analysis might be biased towards advanced disease and that the precise stage at which regions become involved could not be ascertained. Our analysis provides an overview of iron deposition in multiple brain regions of PD patients, and a comparison of outcomes from different methods detecting levels of iron.

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Higher iron in the red nucleus marks Parkinson's dyskinesia

Cited by 78 publications

References 45 publications

Association between increased magnetic susceptibility of deep gray matter nuclei and decreased motor function in healthy adults

Association between increased magnetic susceptibility of deep gray matter nuclei and decreased motor function in healthy adults

On the neuronal circuitry mediating l-DOPA-induced dyskinesia

Meta-analysis of brain iron levels of Parkinson’s disease patients determined by postmortem and MRI measurements

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