Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Blocking enzyme found to ease anxiety without causing sedation

02.10.2002


Suggests new route to treat anxiety without sedating or addicting side effects



The trouble with most anti-anxiety drugs is that they tend to sedate, not just relax. A research team led by scientists at UCSF’s Ernest Gallo Clinic and Research Center has shown that de-activating a common enzyme in neurons reduces anxiety without inducing sedation. The study in mice suggests a new route to treat anxiety while avoiding sedating and possibly addicting effects.

The research, published in the October issue of The Journal of Clinical Investigation, also showed that blocking the enzyme reduced levels of stress hormones. The same issue of the journal includes a commentary on the research (Anxiolytic Drug Targets: Beyond the Usual Suspects) by Joshua A. Gordon of Columbia University’s Center for Neurobiology and Behavior.


Anti-anxiety drugs such as Valium often leave people sedated, less capable at mental tasks, and can become addicting, whereas drugs without these side effects -- such as some antidepressants -- may not reduce anxiety as well, said Robert Messing, MD, UCSF professor of neurology at the Gallo Research Center and senior author on the paper.

But in the new study, mice lacking the enzyme showed reduced anxiety while maintaining normal levels of alertness and learning abilities, the researchers reported.

The enzyme, known as protein kinase C epsilon (PKC epsilon), is present in many neurons in the brain, but its role is not well known. Its ability to affect anxiety but not sedation may stem from indirect, rather than direct action, the researchers found.

When the neurotransmitter GABA binds to proteins on the surface of many neurons, known as GABA-A receptors, the neurons become less active, which tends to reduce anxiety. Drugs such as Valium act by increasing the action of GABA at the GABA-A receptors. A group of brain molecules derived from progesterone, known as neurosteroids, also act to increase the action at the GABA-A receptor, and thereby reduce anxiety. But PKC epsilon appears to make the GABA-A receptor less sensitive to the neurosteroids, increasing anxiety. Experiments using brain membranes and studies of mouse behavior showed that knocking out PKC epsilon increases GABA-A receptor sensitivity to neurosteroids, and thereby decreases anxiety.

"PKC modulates the modulator," Messing said. Because it is an intermediary, it is a promising focus for drugs that could decouple the biochemical pathway that leads to anxiety from the pathway that leads to sedation, he said.

The researchers focused on physiological and behavioral effects of knocking out the PKC gene. Messing and his colleagues developed the strain of PKC knockout mice in 1998 and have been studying the neurological effects.

In tests that measure the tendency of mice to avoid heights and exposed environments, the research showed that PKC epsilon-knockout mice expressed less anxiety-like behavior than wild-type mice. The mice also had lower levels of the stress hormone corticosterone. When GABA-A receptor activity was chemically blocked, anxiety and stress hormone levels increased to normal.

Other studies by Messing and colleagues have shown that knocking out the PKC epsilon gene reduces pain related to inflammation and decreases consumption of alcohol in mice. Work by others indicates that knocking out PKC epsilon reduces fertility of female mice by weakening their immune function. But a drug designed to inhibit PKC epsilon might well avoid this side effect, since it would not knock out all enzyme function, Messing noted.

"Although we don’t yet know precisely how PKC epsilon normally affects GABA-A receptors, the research clearly shows its effect on anxiety-related behavior," Messing said. "A drug based on this finding may well treat anxiety without compromising alertness or cognitive abilities."

Wallace Ravven | EurekAlert!
Further information:
http://www.ucsf.edu/

More articles from Health and Medicine:

nachricht Tracking movement of immune cells identifies key first steps in inflammatory arthritis
23.01.2017 | Massachusetts General Hospital

nachricht Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

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...

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

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>