Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Drug treatment improves learning in mice with Down syndrome symptoms

A once-a-day, short-term treatment with a drug compound substantially improved learning and memory in mice with Down syndrome symptoms, say researchers at the Stanford University School of Medicine and Lucile Packard Children’s Hospital.

What’s more, the gains lasted for months after the treatment was discontinued. The researchers are now considering a clinical trial to test whether the compound has a similar effect in humans with Down syndrome.

"This treatment has remarkable potential," said Craig Garner, PhD, professor of psychiatry and behavioral sciences and co-director of Stanford’s Down Syndrome Research Center. "So many other drugs have been tried that had no effect all. Our findings clearly open a new avenue for considering how cognitive dysfunction in individuals with Down syndrome might be treated." The center was created by researchers at Stanford and Packard Children’s in 2003 to rapidly translate research discoveries into useful treatments for people with Down syndrome.

The research, which will be published Feb. 25 in the advance online edition of Nature Neuroscience, was conducted by Fabian Fernandez, a graduate student in Garner’s laboratory. Fernandez found that affected mice were significantly better able to identify novel objects and navigate a maze ­ tasks that simulate difficulties faced by children and adults with Down syndrome ­ after being fed 17 daily doses of milk containing a compound called pentylenetetrazole, or PTZ. Treated mice performed as well as their wild-type counterparts for up to two months after drug treatment was discontinued.

... more about:
»Fernandez »PTZ »compound »doses »excitation »wild-type

"Somehow the drug treatment creates a new capacity for learning," said Garner, who cautions that this new ability may decay over longer periods of time as older, drug-experienced neurons are replaced by younger cells.

The researchers believe that the key to the improvement lies in the fact that PTZ blocks the action of an inhibitory neurotransmitter called GABA. Normal 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 the 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 both strongly cautioned individuals against experimenting with the compound or others like it on their own. Appropriate doses and schedules have not yet been determined for humans, and the purity and safety of similar over-the-counter concoctions are questionable. Finally, they emphasized that PTZ treatment did not improve the learning capabilities of normal mice.

"We’re not in the business of cognitive enhancement," said Fernandez. "Basically, we have something that could be one part of the many different medical and environmental interventions that may allow kids with Down syndrome to live more normally."

Louis Bergeron | EurekAlert!
Further information:

Further reports about: Fernandez PTZ compound doses excitation wild-type

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Greater Range and Longer Lifetime

26.10.2016 | Power and Electrical Engineering

VDI presents International Bionic Award of the Schauenburg Foundation

26.10.2016 | Awards Funding

3-D-printed magnets

26.10.2016 | Power and Electrical Engineering

More VideoLinks >>>