Sahil Chawla1, Seema Gulyani2, Richard P Allen3, Christopher J Earley3, Xu Li4, Peter Van Zijl4, Dimitrios Kapogiannis1. 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
STUDY OBJECTIVES: Determine abnormalities in levels of iron-management proteins in neuronal origin-enriched extracellular vesicles (nEVs) in restless legs syndrome (RLS). METHODS: We 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. RESULTS: RLS 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. CONCLUSIONS: Given the neuronal origin and diversity of EV cargo, nEVs provide an important platform for exploring the underlying pathophysiology and possible biomarkers of RLS. Published by Oxford University Press on behalf of Sleep Research Society (SRS) 2019.
STUDY OBJECTIVES: Determine abnormalities in levels of iron-management proteins in neuronal origin-enriched extracellular vesicles (nEVs) in restless legs syndrome (RLS). METHODS: We 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. RESULTS: RLS 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. CONCLUSIONS: Given the neuronal origin and diversity of EV cargo, nEVs provide an important platform for exploring the underlying pathophysiology and possible biomarkers of RLS. Published by Oxford University Press on behalf of Sleep Research Society (SRS) 2019.
Entities:
Keywords:
exosomes; extracellular vesicles; ferritin; iron; restless legs syndrome
Authors: J Fauré; G Lachenal; M Court; J Hirrlinger; C Chatellard-Causse; B Blot; J Grange; G Schoehn; Y Goldberg; V Boyer; F Kirchhoff; G Raposo; J Garin; R Sadoul Journal: Mol Cell Neurosci Date: 2006-01-30 Impact factor: 4.314
Authors: Edward J Goetzl; Dimitrios Kapogiannis; Janice B Schwartz; Iryna V Lobach; Laura Goetzl; Erin L Abner; Gregory A Jicha; Anna M Karydas; Adam Boxer; Bruce L Miller Journal: FASEB J Date: 2016-09-06 Impact factor: 5.191
Authors: Christopher J Earley; James Connor; Diego Garcia-Borreguero; Peter Jenner; John Winkelman; Phyllis C Zee; Richard Allen Journal: Sleep Med Date: 2014-06-16 Impact factor: 3.492
Authors: Pavan Bhargava; Carlos Nogueras-Ortiz; Sol Kim; Francheska Delgado-Peraza; Peter A Calabresi; Dimitrios Kapogiannis Journal: Mult Scler Date: 2020-06-17 Impact factor: 6.312
Authors: Dean Tran; Phillip DiGiacomo; Donald E Born; Marios Georgiadis; Michael Zeineh Journal: Front Hum Neurosci Date: 2022-07-13 Impact factor: 3.473