TY - JOUR
T1 - Thy1 expression in the brain is affected by iron and is decreased in Restless Legs Syndrome
AU - Wang, Xinsheng
AU - Wiesinger, Jason
AU - Beard, John
AU - Felt, Barbara
AU - Menzies, Sharon
AU - Earley, Christopher
AU - Allen, Richard
AU - Connor, James
N1 - Funding Information:
The authors are grateful to the Restless Legs Syndrome Foundation for access to the RLS Brain Donation Center. This work was supported in part by NIH grant, NS042857, NS35088 and with Tobacco Settlement funds under a grant with the Pennsylvania Department of Health. The Department specifically disclaims responsibility for any analyses, interpretations or conclusions. Sharon Menzies died shortly after the completion of this study. The authors mourn her loss.
PY - 2004/5/15
Y1 - 2004/5/15
N2 - Thy-1 is a cell adhesion molecule that plays a regulatory role in the vesicular release of neurotransmitters. The objective of this study is to examine the relationship between iron status and Thy1 expression in neuronal systems of varying complexity. Pheochromocytoma cell (PC12) cells were used to explore whether there was a direct relation between cellular iron status and Thy1 expression. Iron chelation significantly decreased expression of Thy1 in PC12 cells in a dose and time dependent manner. Transferrin receptor expression was increased with iron chelation demonstrating that a global decrease in protein synthesis could not account for the Thy1 changes. We also examined brain homogenates from adult rats that were nursed by dams on an iron deficient (ID) diet and found a significant decrease in Thy1 compared to control rats. Finally, the substantia nigra from individuals with Restless Legs Syndrome reportedly has lower than normal amounts of iron. Therefore, we examined this brain region from individuals with the clinical diagnosis of primary Restless Legs syndrome (RLS) and found the concentration of Thy1 was less than half that of controls. The results of these studies support the novel concept that there is a relationship between Thy1 and iron and point to a novel mechanism by which iron deficiency can affect brain function. They also indicate a possible mechanism by which iron deficiency compromises dopaminergic transmission in RLS, providing a potentially important link between decreased brain iron and the responsiveness to levodopa and iron supplementation treatment in RLS.
AB - Thy-1 is a cell adhesion molecule that plays a regulatory role in the vesicular release of neurotransmitters. The objective of this study is to examine the relationship between iron status and Thy1 expression in neuronal systems of varying complexity. Pheochromocytoma cell (PC12) cells were used to explore whether there was a direct relation between cellular iron status and Thy1 expression. Iron chelation significantly decreased expression of Thy1 in PC12 cells in a dose and time dependent manner. Transferrin receptor expression was increased with iron chelation demonstrating that a global decrease in protein synthesis could not account for the Thy1 changes. We also examined brain homogenates from adult rats that were nursed by dams on an iron deficient (ID) diet and found a significant decrease in Thy1 compared to control rats. Finally, the substantia nigra from individuals with Restless Legs Syndrome reportedly has lower than normal amounts of iron. Therefore, we examined this brain region from individuals with the clinical diagnosis of primary Restless Legs syndrome (RLS) and found the concentration of Thy1 was less than half that of controls. The results of these studies support the novel concept that there is a relationship between Thy1 and iron and point to a novel mechanism by which iron deficiency can affect brain function. They also indicate a possible mechanism by which iron deficiency compromises dopaminergic transmission in RLS, providing a potentially important link between decreased brain iron and the responsiveness to levodopa and iron supplementation treatment in RLS.
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U2 - 10.1016/j.jns.2004.02.004
DO - 10.1016/j.jns.2004.02.004
M3 - Article
C2 - 15140607
AN - SCOPUS:2442553766
VL - 220
SP - 59
EP - 66
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510X
IS - 1-2
ER -