Down Syndrome Brain Function Improved In Mice

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Main Category: Neurology / Neuroscience
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Article Date: 26 Feb 2007 - 0:00 PDT

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US scientists have discovered that an old discontinued drug reduces the mental retardation of mice with a form of Down syndrome.

The study is published in the latest online edition of the journal Nature Neuroscience.

The research was led by Professor of Psychiatry and Director of the Down Syndrome Research Centre at Stanford University in California, Craig Garner.

Garner and his team used Ts65Dn mice bred as a model for Down syndrome and gave them an old discontinued drug that was once used to study epilepsy in humans.

Ts65Dn mice are known to have excessive inhibition of the dentate gyrus, a part of the brain around the hippocampus that is important to learning and memory.

The mice improved their ability to explore, learn and remember things. For example when given a T-shaped maze to explore, at first they explored it in a random fashion, but after 17 days they were exploring one arm first, like normal mice.

The effects of the drug persisted for two months after it was stopped.

The drug is called pentylenetetrazole or PTZ, a GABAA antagonist. GABAA are receptors that control the ability of neurons to "fire" and make connections with each other, a process that is fundamental to learning and memory.

People with Down syndrome or "trisomy 21" have an extra complete or partial copy of chromosome 21, whereas most people have two. It can usually be spotted at birth and is characterized by facial and body structure differences. Symptoms include some impairment of physical and cognitive development, including heart problems.

About one in every 800 children born around the world have Down syndrome. The prevalence is the same across ethnic and socioeconomic groups. Older mothers have a higher risk of having babies with Down syndrome, rising from one in 1,000 in their twenties to one in 11 at the age of 49.

As a result of this study, Garner and his team suggest that over-inhibition of neuronal excitation contributes to the intellectual disability associated with Down syndrome and that GABAA antagonists, of which PTZ is one example, could be developed to treat the disorder.

Applying this knowledge to humans will not be straightforward. In large doses PTZ causes epileptic seizures. The Food and Drug Administration withdrew approval for its use in the 1980s. And many drugs that show improved learning and cognitive functioning in mice do not work with humans.

"Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome."
Fabian Fernandez, Wade Morishita, Elizabeth Zuniga, James Nguyen, Martina Blank, Robert C Malenka and Craig C Garner.
Nature Neuroscience Published online: 25 February 2007
doi:10.1038/nn1860

Click here for Abstract.

Click her for Down Syndrome Research and Treatment Foundation.

Written by: Catharine Paddock
Writer: Medical News Today
Copyright: Medical News Today
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