Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Rice University study finds possible clues to epilepsy, autism

10.12.2008
Rice University researchers have found a potential clue to the roots of epilepsy, autism, schizophrenia and other neurological disorders.

While studying the peripheral nerves of the Drosophila, aka the fruit fly, Rice doctoral student Eric Howlett discovered an unanticipated connection between glutamate – an amino acid and neurotransmitter in much of the food we eat – and phosphoinositide 3-kinase (PI3K), an enzyme that, Howlett found, regulates the activity of neurons.

Howlett and his colleagues, graduate student Curtis Chun-Jen Lin, research technician William Lavery and Michael Stern, a professor of biochemistry and cell biology, discovered that negative feedback mediated by PI3K regulates the excitability of neurons, an issue in a number of ailments that include neurofibromatosis, and that a mutation in a glutamate receptor gene common to both the fruit fly and humans has the ability to disrupt that regulatory mechanism.

Howlett found the Drosophila’s metabotropic glutamate receptor (DmGluRA) gene, when mutated, increased the excitability of the neuron by preventing PI3K from doing its job.

Published online by the Public Library of Science Genetics, the study is the culmination of four years of work that built upon research by Marie-Laure Parmentier and her team at the University of Montpelier, France, to connect glutamate to regulatory functions in the fruit fly.

“As science often goes, we didn’t set out with this hypothesis,” said Howlett, who began the project on funding obtained by Stern from the Department of Defense to study neurofibromatosis. “This all came about as a control for a completely different experiment, and we said, ‘Wow, this is some interesting stuff.’”

What he saw was that the overexpression of PI3K in motor neurons had a dramatic effect. “I noticed under the scope that these nerves were really big, and electrophysiologically, they were really slow. That wasn’t what I expected, and it set me on a path of trying to find out what was going on.”

Howlett’s breakthrough was identifying the negative feedback loop that acts to maintain neuronal excitability at normal levels. “What we found was that glutamate, which is released due to neuronal activity, feeds back onto metabotropic glutamate receptors on the same neurons that released it in the first place. This leads to the activation of PI3K and ultimately to the dampening of the amount of glutamate that is released.” Without that regulation, he said, things inside the cell can go terribly wrong.

“He put his heart and soul into this,” said Stern of Howlett’s exploration of the neuronal chain. “He was working on PI3K because that has a key role in neurofibromatosis. The Department of Defense is very interested in how PI3K is regulated in the nervous system because of its role in tumor formation.”

Discovering the negative feedback loop that keeps neurons stable was key, said Stern, but not the end of the investigation. “We know that glutamate activates mGluR and PI3K, but we don’t know how,” he said. “There are almost certainly a number of intermediates that remain to be identified, and we have several candidates we’re looking into.

“We’re finding a mechanistic link among these molecules that hadn’t been previously appreciated,” Stern said.

“Obviously the next step would be to test whether these same molecules are playing similar roles in mammalian neurons,” said Howlett, who will leave Rice in the spring to pursue postdoctoral cancer research at Virginia Commonwealth University. A native Houstonian, he earned his bachelor’s in biology at the University of Houston-Clear Lake.

Howlett said mGluRs had already been targeted in possible treatments for schizophrenia, epilepsy and other “excitability” diseases, so it’s not a stretch to think his research could lead to even more strategies in treating neurological ailments.

“Actually, all of the molecules involved in our model have been implicated in one way or another with neurological diseases, but no one has been able to link them together into a coherent explanation of the diseases,” he said. “Our model provides a novel framework that could really go a long way toward doing that.”

The paper can be found at: www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1000277.

David Ruth | EurekAlert!
Further information:
http://www.rice.edu

More articles from Life Sciences:

nachricht Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Superconducting vortices quantize ordinary metal

Russian researchers together with their French colleagues discovered that a genuine feature of superconductors -- quantum Abrikosov vortices of supercurrent -- can also exist in an ordinary nonsuperconducting metal put into contact with a superconductor. The observation of these vortices provides direct evidence of induced quantum coherence. The pioneering experimental observation was supported by a first-ever numerical model that describes the induced vortices in finer detail.

These fundamental results, published in the journal Nature Communications, enable a better understanding and description of the processes occurring at the...

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Rapid water formation in diffuse interstellar clouds

25.06.2018 | Physics and Astronomy

Using tree-fall patterns to calculate tornado wind speed

25.06.2018 | Earth Sciences

'Stealth' material hides hot objects from infrared eyes

25.06.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>