Mitochondrial ferritin in the substantia nigra in restless legs syndrome.
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.
Snyder
Amanda M
AM
Department of Neurosurgery, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Wang
XinSheng
X
Patton
Stephanie M
SM
Arosio
Paolo
P
Levi
Sonia
S
Earley
Christopher J
CJ
Allen
Richard P
RP
Connor
James R
JR
D000368:Aged; D000369:Aged, 80 and over; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005293:Ferritins / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism; D000090463:Iron Deficiencies; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D012148:Restless Legs Syndrome / Q000378:metabolism* / Q000473:pathology; D013378:Substantia Nigra / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology
D024101:Mitochondrial Proteins; D005293:Ferritins; D007501:Iron