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Biological Chemistry

Potential Down Syndrome Therapy Works In Mice

A norepinephrine precursor helps reverse learning and memory difficulties in lab studies

by Sophie L. Rovner
November 23, 2009 | A version of this story appeared in Volume 87, Issue 47

If results from a study in mice can be extended to people, it’s possible that cognitive problems associated with Down syndrome could be ameliorated with a simple drug treatment (Sci. Transl. Med. 2009, 1, 7ra17). Children with Down syndrome—the most common cause of mental retardation—aren’t developmentally delayed at birth, but over time they develop difficulties with learning and memory. These cognitive abilities depend on the hippocampus, which receives input from other regions of the brain, including the locus coeruleus. The locus coeruleus communicates with the hippocampus by means of the neurotransmitter norepinephrine. Ahmad Salehi of Stanford University School of Medicine and colleagues studied mice genetically engineered to mimic Down syndrome and found that the locus coeruleus degenerates—just as it does in humans with the condition. The researchers also showed that the hippocampal neurons that are the target of the locus coeruleus’ norepinephrine signaling remain functional. They determined that the mice could overcome their learning difficulties when dosed with a phenylserine norepinephrine precursor (shown above), raising the possibility that enhancing norepinephrine neurotransmission in people with Down syndrome might reverse cognitive dysfunction as well.


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