Thy1 expression in the brain is affected by iron and is decreased in Restless Legs Syndrome.
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.
Wang
Xinsheng
X
Department of Neural and Behavioral Science (H109), Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Wiesinger
Jason
J
Beard
John
J
Felt
Barbara
B
Menzies
Sharon
S
Earley
Christopher
C
Allen
Richard
R
Connor
James
J
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count; D003676:Deferoxamine / Q000494:pharmacology; D004032:Diet / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007501:Iron / Q000502:physiology*; D007502:Iron Chelating Agents / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D011990:Receptors, Transferrin / Q000378:metabolism; D012148:Restless Legs Syndrome / Q000378:metabolism*; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism*; D018800:Thy-1 Antigens / Q000378:metabolism*; D013997:Time Factors
D007502:Iron Chelating Agents; D011990:Receptors, Transferrin; D018800:Thy-1 Antigens; D020932:Nerve Growth Factor; D007501:Iron; D003676:Deferoxamine