Extracellular vesicles reveal abnormalities in neuronal iron metabolism in restless legs syndrome

Author:

Chawla Sahil1,Gulyani Seema2,Allen Richard P3,Earley Christopher J3,Li Xu4,Van Zijl Peter4,Kapogiannis Dimitrios1ORCID

Affiliation:

1. Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD

2. Johns Hopkins Sleep Disorders Center, Johns Hopkins Bayview Medical Center, Baltimore, MD

3. Department of Neurology, The Johns Hopkins Center for Restless Legs Syndrome, Johns Hopkins Bayview Medical Center, Baltimore, MD

4. Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins Medicine, Baltimore, MD

Abstract

AbstractStudy ObjectivesDetermine abnormalities in levels of iron-management proteins in neuronal origin-enriched extracellular vesicles (nEVs) in restless legs syndrome (RLS).MethodsWe used immunoprecipitation for neuronal marker L1CAM to isolate nEVs from the serum of 20 participants with RLS from a study including magnetic resonance imaging (MRI) determinations of iron deposition in the substantia nigra and hematologic parameters and 28 age- and sex-matched Controls.ResultsRLS compared with Control participants showed higher levels of nEV total ferritin but similar levels of transferrin receptor and ferroportin. Western blot analysis showed that heavy- but not light-chain ferritin was increased in nEVs of RLS compared with Control participants. In RLS but not Control participants, nEV total ferritin was positively correlated with systemic iron parameters; the two groups also differed in the relation of nEV total ferritin to MRI measures of iron deposition in substantia nigra.ConclusionsGiven the neuronal origin and diversity of EV cargo, nEVs provide an important platform for exploring the underlying pathophysiology and possible biomarkers of RLS.

Funder

National Institutes of Health

National Institute on Aging

NIH

Publisher

Oxford University Press (OUP)

Subject

Physiology (medical),Clinical Neurology

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