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Dopamine D2 receptors are decreased in the brains of RLS patients, and the extent of the decrease correlates with severity of symptoms, according to a new study. The results confirm the importance of aberrant dopamine signaling in RLS, and support the role of a primary iron insufficiency in RLS pathogenesis. Brains from 8 RLS patients and 15 age- and sex-matched controls were examined. RLS patients' age at death ranged from 53 to 84 years, with disease duration ranging from 32 to 78 years. Patients had reported daily RLS symptoms, with IRLSS scores averaging 31 (severe). In the putamen, expression of D2 receptors was approximately 30% reduced (p=0.028) compared to controls, with no difference in D1 receptors, dopamine transporter, VMAT, or dopamine. The expression level of putaminal D2 receptors decreased linearly with severity of RLS symptoms, such that the most affected patient had only 25% of the receptors as the least affected patient. These results support the "clinical evidence that alterations in the dopaminergic system may underlie the symptoms associated with RLS," the authors state. Tyrosine hydroxylase and phosphorylated (active) TH (pTH) were both elevated, in both the putamen and the substantia nigra. The authors note they were surprised by this result, since it "had not been anticipated as a consequence of iron deficiency," which is believed to contribute to RLS pathogenesis. Consequently, the authors explored the effect on TH and pTH in rat and cell models of iron deficiency. The TH and pTH elevations were observed in both systems. "The particularly striking aspect of these.new results," the authors conclude, is "the surprising discovery that iron deficiency and RLS both appear to produce states that would be essentially associated with increased dopaminergic activity," and support the concept that the RLS brain is iron deficient. Altered dopaminergic profile in the putamen and substantia nigra in restless legs syndrome JR Connor, XS Wang, RP Allen, JL Beard, JA Wiesinger, BT Felt, CJ Earley Brain 2009;132:2403-2412 ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn