Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

ADHD: A gene makes fish larvae hyperactive

25.09.2012
Many genes are suspected of being involved in the development of attention deficit hyperactivity disorder (ADHD). A Franco-German research group has now examined the role of one of these more closely and discovered clear indications of its complicity.
Its scientific name is lphn3. In humans, this gene lies on chromosome 4 and codes the protein latrophilin 3, which may play a role as a synaptic protein and receptor in the brain when the typical characteristics of attention deficit hyperactivity disorder emerge: people affected struggle to focus their attention over longer periods, they are easily distracted, they tire quickly, they often react impulsively, and they demonstrate obvious motor restlessness.

Focus on the latrophilin 3 gene

“Latrophilin 3 has long been suspected of being partly responsible for the typical characteristics of ADHD. Though, not all that much is known to date about its role within the physiological processes of the nervous system,” says Professor Klaus-Peter Lesch.
Lesch is Chairman of the Department of Molecular Psychiatry and Spokesman for the ADHD Clinical Research Group at the University of Würzburg’s Department of Psychiatry, Psychosomatics, and Psychotherapy. He has had his sights on this protein for a few years now. And he is not alone: “Researchers from the USA and Spain have recently shown that a particular variant of the latrophilin 3 gene is frequently found in the genetic material of patients who are still suffering from ADHD in adulthood,” says Lesch. What is more, the gene has also been identified as one of a total of 86 risk genes that are suspected of triggering drug dependency. The occurrence of drug dependency is above average in ADHD patients.

Experiments on zebrafish larvae

To improve understanding of the role that latrophilin 3 plays in the development of ADHD symptoms, Lesch and scientists from the Institute of Neurobiology in Gif-sur-Yvette, France, conducted experiments with zebrafish larvae. “Zebrafish have now become the standard model in science for examining the genetic fundamentals of brain development and behavior,” explains Lesch.

In their experiments, the researchers inhibited the lphn3 gene during a particular development phase and then examined the behavior of the fish larvae. They concentrated primarily on the movement activity of the larvae as an easily measurable expression of motor restlessness.
The results

The outcome: “We observed a significant increase in swimming distances and average speed in these fish larvae compared to a control group,” write the authors. This effect was also evident during the night-time sleep phases – in the same way as human ADHD patients can demonstrate hyperactivity symptoms in their sleep.

The scientists believe that this increased urge to move was caused by a fault in the development of the neural networks of the dopamine system in the brain of the zebrafish larvae. Dopamine is a transmitter that is responsible for, among other things, making movements happen harmoniously and optimizing certain mental processes. The larvae in which the lphn3 gene had been inhibited consequently developed considerably fewer nerve cells that produce dopamine. The more pronounced the urge to move was in the fish, the lower the number was of these specific neurons.

Methylphenidate helps

If zebrafish demonstrate symptoms typical of ADHD under these conditions, can they too be treated with the usual medications? This question was also explored by the researchers. One of the most effective drugs for treating ADHD in humans is methylphenidate – better known in Germany under the brand name Ritalin. This amphetamine-like substance affects the metabolism of dopamine; it is designed to increase attention and perception and to reduce psychomotor activity and impulsiveness.

When administered to the zebrafish larvae, methylphenidate demonstrated similar results: the larvae did not swim anywhere near the distances that they had been covering before. Their speed also reduced considerably – to that of “normal”, untreated larvae.

The authors draw two consequences from the results of this study: firstly, the findings clearly show the importance of the lphn3 gene to the development of the dopaminergic signaling pathway in the embryonic phase. Secondly, they demonstrate that reduced lphn3 functionality in zebrafish larvae causes typical changes in behavior that are very similar to the usual characteristics of ADHD.

About ADHD

According to the latest estimates, between three and seven percent of all children suffer from attention deficit hyperactivity disorder (ADHD). Boys are around four times more likely to be affected than girls. Contrary to popular belief, adults can also suffer from ADHD; around four percent apparently show typical symptoms.

Those affected are usually hyperactive and possess an increased urge to move, they tend to be more impulsive, and they find it hard to concentrate. For this reason, children and young people often experience difficulties in education and training; adult sufferers frequently have problems in their careers and relationships.

The genetic component in the development of ADHD is estimated at 70 to 80 percent. But environmental influences can also mitigate or exacerbate the symptoms. Cigarettes and alcohol during pregnancy increase the risk, as does a premature birth or a low birth weight.

The ADHD-susceptibility gene lphn3.1 modulates dopaminergic neuron formation and locomotor activity during zebrafish development; M Lange, W Norton, M Coolen, M Chaminade, S Merker, F Proft, A Schmitt, P Vernier, K-P Lesch and L Bally-Cuif. Molecular Psychiatry 2012, 17:946-54, doi:10.1038/mp.2012.29.

Contact

Prof. Dr. Klaus-Peter Lesch,
T: +49 (0)931 201-77600, e-mail: kplesch@mail.uni-wuerzburg.de

Gunnar Bartsch | Uni Würzburg
Further information:
http://www.uni-wuerzburg.de

More articles from Life Sciences:

nachricht Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)

nachricht CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New Study Will Help Find the Best Locations for Thermal Power Stations in Iceland

19.01.2017 | Earth Sciences

Not of Divided Mind

19.01.2017 | Life Sciences

Molecule flash mob

19.01.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>