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 BigH1 -- The key histone for male fertility
14.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Guardians of the Gate
14.12.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Plasmonic biosensors enable development of new easy-to-use health tests

14.12.2017 | Health and Medicine

New type of smart windows use liquid to switch from clear to reflective

14.12.2017 | Physics and Astronomy

BigH1 -- The key histone for male fertility

14.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>