Saturday, November 21, 2009

Down but not Out -- Possible cure for Down's -Syndrome?


Restoration of Norepinephrine-Modulated Contextual Memory in a Mouse Model of Down Syndrome

 Sci Transl Med, 18 November, 2009:
Vol. 1, Issue 7,
p. 7ra17


from Google-Images

Down's syndrome: condition caused by the trisomy of the 21st chromosome. 

A recent paper in "Science Translational Medicine" talks of a possible hope, over the horizon, for patients, after some extremely positive results with experiments on mice.

Gen/Pheno-type of the 'Down'-Mice: The Ts65Dn mouse model has a 'humanised'-trisomy (an extra, third copy of 104 genes on chromosome 16 that are homologous to genes on human chromosome 21). and is known to show abnormal responses in behavioral tests for contextual learning. They don't respond to fear conditioning. Also, when provided with material to build nests, they create shabbier homes reflecting their decreased ability to respond to new contexts.

The study: Incidentally a significant neurodegeneration takes place in the locus coeruleus (LC), an area of the brain which produces and supplies the hippocampus (and other parts of the brain), with the neurotransmitter norepinephrine, essential for learning and memory function. That finding corroborated with the fact that the LC also degenerates in humans with Down syndrome.

Since the locus coeruleus produces norepinephrine, the group then figured out how that neurotransmitter comes into play. Upon injection of the trisomy mice with l-DOPS (l-threo-3,4-dihydroxyphenylserine, or xamoterol, a β1-adrenergic receptor partial agonist), a drug that can cross the blood-brain barrier and convert into norepinephrine, the mice significantly improved their performance in tests of both fear conditioning and nest-building, behaving more like the normal animals.

When the drug wore off, so too did the mutants' improved nest-building ability.

The LC degeneration  in the trisomy mice doesn't just affect humans with Down syndrome, it is also significantly observed in individuals with Alzheimer's disease and other types of dementia. Incidentally, as many as 25% or more people with Down syndrome go on to develop Alzheimer's-type dementia.
This link may arise via the an increased gene dosage of App, on chromosome 21, which codes for the amyloid precursor protein, and which was found to be necessary for locus coeruleus degeneration.

Hope from the study: This study shows thet even in presence of LC-degeneration, one can still rescue the function in the brain, albeit temporarily.
Surely, of course, future studies will essentially need to explore the optimum drug and dosage that can enhance the production of norepinephrine in the 'damaged' area of the brain.

________________________________________________________________________________                                                                                                                               a li'l adapted from 'The-Scientist'

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