Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Cognitive dysfunction reversed in mouse model of Down syndrome

A study by neuroscientist William C. Mobley, MD, PhD, chair of the Department of Neurosciences at the University of California, San Diego School of Medicine, and colleagues at Stanford University Medical School has demonstrated a possible new approach to slowing the inevitable progression of cognitive decline found in Down's syndrome.

The study, published in Science Translational Medicine on November 18, revealed two important new findings about Down's syndrome in a mouse model: 1) there is evidence that synaptic terminals involved in neurotransmission are damaged long before the cells show degeneration; and 2) while cell signaling is damaged, the receptors are not, but are functioning and still trying to find signals.

"If we focus only on damage to cell bodies, we underestimate the importance of timing and the potential window for treatment of Down's syndrome," said Mobley, one of the nation's leading experts in the disease. He added that this study in mice shows some of the early changes to neurons, which are "really quite dramatic," and may point the way to novel ways to treat Down's syndrome in adult patients.

Down's syndrome is a chromosomal disorder caused by the presence of all or part of an extra 21st chromosome, resulting in marked deficits in contextual learning and memory. Fifty years ago, the disorder was identified as a chromosome 21 trisomy, meaning that each cell in the body has three copies of chromosome 21 instead of the usual two.

Individuals with Down's syndrome tend to have a lower than average cognitive ability, and most who survive into middle age begin to show Alzheimer's-like dementia by age 50 or 60. The incidence of Down's syndrome is estimated at one in 733 live births in the U.S., or 5,000 affected infants each year; approximately 95% of these are trisomy 21. Until quite recently, it wasn't believed that scientists would ever be able to pinpoint the exact gene or genes that cause the disease.

The research team studied a mouse model with three copies of a fragment of mouse chromosome 16, having symptoms very similar to those in humans with Down's syndrome. Symptoms included significant cognitive deficits and dysfunction and degeneration of LC neurons (with origination in locus coeruleus). These damaged neurons use norepinephrine, which is a neurotransmitter, to pass impulses to receptors in the cortex and hippocampus – brain regions critical for learning, memory and attention.

"We found that, despite advanced LC degeneration, we could reverse contextual learning failure in these mice," said Mobley. Using a pro-drug for norepinephrine called L-DOPS or xamoterol, the scientists were able to restore neurotransmission in the mice, thus rescuing cognition. While it is yet to be determined if LC plays a role in contextual learning in humans, scientists know that these neurons are affected in other neurodegenerative diseases, including Alzheimer's disease.

In addition, the team identified the gene fragment in mice that is largely responsible for LC degeneration – a region of about 32 genes including APP 23, 24. In a knockout mouse model with the third copy of APP deleted, the decrease in LC neurons did not occur, suggesting that App over-expression is necessary for LC degeneration. However, deleting the extra copy did not restore normal contextual learning behavior.

"Simply deleting the third App doesn't fix the behavior, so probably other gene products play a role in Down's syndrome," said Mobley. "However, giving the pro-drug to the mice rescued cognitive behaviors in a very dramatic way."

He noted that a form of this drug is currently in clinical trials to treat fibromyalgia in humans. "The possibility is very real that such a therapy, if proven safe, would be effective in treating dementia in later-stage Down's syndrome patients."

Additional contributors include Paul Aisen and Steven L. Wagner, UC San Diego Department of Neurosciences; and A. Salehi, M. Faizi, D. Colas, J. Valletta, J. Laguna, R. Takimoto-Kimura, A. Kleschevnikov and M. Shamloo, Stanford University.

The work was supported by the National Institutes of Health, the Larry L. Hillblom Foundation, the Down's Syndrome Research and Treatment Foundation, the Thrasher Research Fund, the Adler Foundation and the Alzheimer's Association.

Please visit after 2 p.m. ET November 18 to view an interview with William Mobley and Steve Wagner of the UC San Diego Department of Neurosciences, discussing these findings.

Debra Kain | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

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

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>