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

Sleep. 2019 Jul 8;42(7):zsz079. doi: 10.1093/sleep/zsz079.

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.

Keywords: exosomes; extracellular vesicles; ferritin; iron; restless legs syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Antigens, CD / blood
  • Cation Transport Proteins / blood
  • Extracellular Vesicles / metabolism*
  • Female
  • Ferritins / blood
  • Humans
  • Iron / metabolism
  • Male
  • Middle Aged
  • Neural Cell Adhesion Molecule L1 / immunology*
  • Neurons / metabolism*
  • Receptors, Transferrin / blood
  • Restless Legs Syndrome / metabolism*
  • Restless Legs Syndrome / physiopathology*
  • Substantia Nigra / metabolism

Substances

  • Antigens, CD
  • CD71 antigen
  • Cation Transport Proteins
  • L1CAM protein, human
  • Neural Cell Adhesion Molecule L1
  • Receptors, Transferrin
  • metal transporting protein 1
  • Ferritins
  • Iron