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Drug treatment improves learning in mice with Down syndrome symptoms, Stanford/Packard study shows

brains maintain a precise ratio between neuronal excitation and inhibition that allows efficient learning. In contrast, it’s thought that Down syndrome patients have too much GABA-related inhibition, making it difficult to process information.

"In general, learning involves neuronal excitation in certain parts of the brain," said Garner. "For example, caffeine, which is a stimulant, can make us more attentive and aware, and enhance learning. Conversely, alcohol or sedatives impair our ability to learn."

But as any overenthusiastic college student can attest, too much caffeine can backfire. The same is true with high doses of PTZ, which can cause seizures. In fact, after some brief, inconclusive studies on cognition enhancement in elderly or mentally impaired people in the 1950s, PTZ has been primarily used for the study of epilepsy in animals. In 1982 the FDA withdrew approval for the use of PTZ in humans because no clear clinical benefit had been established. That is, until now.

"My idea was that it might be possible to harness this excitation effect, which at higher doses can be pathological, to benefit people with Down syndrome," said Fernandez.

More than 300,000 people nationwide have Down syndrome, which is caused by an extra copy of chromosome 21. It is the leading cause of mental retardation in the country, and it is also associated with childhood heart disease, leukemia and early onset Alzheimer’s disease. The researchers used a mouse model of Down syndrome for their study in which about 150 genes are triplicated. The mice exhibit many of the cognitive problems that afflict human Down syndrome patients.

Fernandez gave low daily doses of PTZ and investigated the animals?responses to unfamiliar objects and a T-shaped maze. In the first example, he allowed the animals to explore two similarly sized, yet obviously different, objects for 15 minutes. Twenty-four hours later he exposed the same animals to one of th
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Source:Stanford University Medical Center


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