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

e previously seen objects and a third, never-before-seen object. Although wild-type mice spent more time investigating the new object, untreated Down syndrome mice showed no preference for either object.

In the maze test, mice were habituated to the long arm of a T-shaped maze and then allowed to explore. Wild-type mice tended to investigate first one, then the other arm of the maze, while untreated Down syndrome mice were less methodical. However, the Down syndrome mice performed more like their wild-type counterparts on both tests after 17 days of PTZ treatment.

The researchers discovered two interesting things when testing the mice: daily doses were required for several days before any effect was detected, and, once established, the effect lasted for up to two months after the drug was withdrawn. In fact, the drug’s activity profile mirrored that of some well-known psychiatric medications.

"This suggests that it’s not just the removal of the excess inhibition that allows learning to occur, but that we’re instead strengthening synapses through some type of long-lasting neuronal adaptation," said Garner.

A key component of enduring neural change associated with memory is known as long-term potentiation. In general terms, once a threshold of activating signals has been achieved, a neuron becomes permanently more sensitive to excitation. Although long-term potentiation has been shown to be impaired or absent in the brains of Down syndrome mice, postdoctoral scholar Wade Morishita, PhD, who works in the Stanford laboratory of professor Rob Malenka, PhD, found that it approached normal levels after chronic PTZ treatment and remained comparable to that in wild-type mice for up to three months after PTZ was discontinued.

PTZ’s history of use in humans is an advantage when planning a clinical trial. However, the compound is not currently approved by the Food and Drug Administration for use in humans. Garner and Fernandez b
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Source:Stanford University Medical Center


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