Abstract
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 language | English |
|---|---|
| Pages (from-to) | 1193-1199 |
| Number of pages | 7 |
| Journal | Journal of Neuropathology and Experimental Neurology |
| Volume | 68 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 2009 |
Fingerprint
Keywords
- Ferritin
- Iron
- Mitochondrion
- Neuron
- Restless leg syndrome
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Clinical Neurology
- Neurology
- Cellular and Molecular Neuroscience
Cite this
Mitochondrial ferritin in the substantia nigra in restless legs syndrome. / Snyder, Amanda M.; Wang, Xinsheng; Patton, Stephanie M.; Arosio, Paolo; Levi, Sonia; Earley, Christopher J.; Allen, Richard P.; Connor, James R.
In: Journal of Neuropathology and Experimental Neurology, Vol. 68, No. 11, 11.2009, p. 1193-1199.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mitochondrial ferritin in the substantia nigra in restless legs syndrome
AU - Snyder, Amanda M.
AU - Wang, Xinsheng
AU - Patton, Stephanie M.
AU - Arosio, Paolo
AU - Levi, Sonia
AU - Earley, Christopher J.
AU - Allen, Richard P.
AU - Connor, James R.
PY - 2009/11
Y1 - 2009/11
N2 - 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.
AB - 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.
KW - Ferritin
KW - Iron
KW - Mitochondrion
KW - Neuron
KW - Restless leg syndrome
UR - http://www.scopus.com/inward/record.url?scp=70449413420&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70449413420&partnerID=8YFLogxK
U2 - 10.1097/NEN.0b013e3181bdc44f
DO - 10.1097/NEN.0b013e3181bdc44f
M3 - Article
C2 - 19816198
AN - SCOPUS:70449413420
VL - 68
SP - 1193
EP - 1199
JO - American Journal of Psychotherapy
JF - American Journal of Psychotherapy
SN - 0002-9564
IS - 11
ER -