Mitochondrial ferritin in the substantia nigra in restless legs syndrome

Amanda M. Snyder, Xinsheng Wang, Stephanie M. Patton, Paolo Arosio, Sonia Levi, Christopher J. Earley, Richard P. Allen, James R. Connor

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61 Scopus citations


Restless legs syndrome (RLS) is a neurological disorder that is thought to involve decreased iron availability in the brain. Iron is required for oxidative metabolism and plays a critical role in redox reactions in mitochondria. The recent discovery of mitochondrial ferritin (FtMt) provided the opportunity to identify a potential correlation between iron and mitochondrial function in RLS. Human substantia nigra (SN) and putamen autopsy samples from 8 RLS cases and 8 controls were analyzed. Mitochondrial ferritin levels in RLS SN tissue homogenate samples assessed by immunoblots had more FtMt than control samples (p < 0.01), whereas there were no significant differences in FtMt in the putamen samples. By immunohistochemistry, neuromelanin-containing neurons in the SN were the predominant cell type expressing FtMt. Staining in neurons in RLS samples was consistently greater than that in controls. Cytochrome c oxidase staining, which reflects numbers of mitochondria, showed a similar staining pattern to that of FtMt, whereas there was less immunostaining in the RLS cases for cytosolic H-ferritin. These results suggest that increased numbers of mitochondria in neurons in RLS and increased FtMt might contribute to insufficient cytosolic iron levels in RLS SN neurons; they are consistent with the hypothesis that energy insufficiency in these neurons may be involved in the pathogenesis of RLS.

Original languageEnglish (US)
Pages (from-to)1193-1199
Number of pages7
JournalJournal of neuropathology and experimental neurology
Issue number11
StatePublished - Nov 2009

All Science Journal Classification (ASJC) codes

  • General Medicine


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