Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Potential treatment for Fragile X Syndrome demonstrated in fruit fly model

03.03.2005


Fragile X Syndrome is one of the most commonly inherited forms of mental retardation, with an incidence of 1 in 4,000 males and 1 in 8,000 females. Not many medications exist to help Fragile X patients. Now, in a fruit fly model of the disease, researchers from the University of Pennsylvania School of Medicine and their colleagues have shown that it is possible to reverse some of the symptoms of the disorder using drugs that dampen specific neuronal overactivity. Their findings appear in the March 3, 2005 issue of Neuron.



Characteristics of Fragile X in people include an average IQ of about 50, deficits in certain types of short-term memory, autistic behavior, sleep problems, hyperactivity, attention deficits, and susceptibility to seizures. In humans, Fragile X syndrome is caused by the FMR1 gene not working properly or at all. This gene encodes the FMRP protein, which controls the availability of select proteins involved in neuron-to-neuron communication.

Senior author Thomas A. Jongens, PhD, Associate Professor of Genetics at Penn, and colleagues from Albert Einstein College of Medicine and Drexel University College of Medicine, as well as other labs, have developed and characterized a Drosophila fly model for Fragile X. This model is based on mutants that lack the dfmr1 gene, which encodes a protein similar to human FMR1 protein. "Interestingly, work by my lab and others have found that the dfmr1 mutants display many physical and behavioral characteristics similar to symptoms displayed by Fragile X patients," says Jongens. These include structural defects in certain neurons, enlarged testes, failure to maintain proper day/night activity patterns; attention deficits and hyperactivity, and defects in behavior-dependent learning and memory.


"Our thinking was that since so many of the behavioral and physical phenotypes in the fly model were similar to symptoms observed in fragile X patients and a mouse fragile X model, FMR1 and dfmr1 must be regulating similar biological processes in human, mice, and flies," states Jongens.

A mouse model of Fragile X also shows symptoms similar to those of Fragile X patients. Studies outside of Penn using the mouse model have demonstrated that Fragile X patients have a tendency to break down synaptic connections (sites used for neuron to neuron communication) more readily than the general population. This breakdown is due to an increased activity in the metabotropic glutamate receptor (mGluR), which is located on the surface of neurons, including in the hippocampus – the memory and learning center in the brain. In turn, this increased activity compromises neurotransmission for memory-associated functions.

Jongens and colleagues surmised that mGluR overactivity may be at the root of many of the Fragile X symptoms. Using such drugs as lithium chloride and others, known as antagonists, that block mGluR’s activity, the team tested to see if the drugs could rescue any of the observed behavioral and memory defects observed in the fly model. "What we found was very striking," says Jongens. They found that the drug treatments restored memory-dependent courtship behavior in mutant flies and reversed some of the neuronal structural defects. The group used lithium because it is known to have activities analogous to blocking mGluR-receptor activity, and it is already an FDA-approved drug used to treat other ailments in humans such as bipolar disorder.

"The big take-home message from our work is that maintaining proper regulation of mGluR signaling is a conserved function of the dFMR1 and FMRP proteins and that loss of dfmr1 function in flies leads to at least a subset of the cognitive and behavioral defects observed in the fly model," says Jongens. "These results provide a potential route by which symptoms of Fragile X patients may be ameliorated."

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>