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/

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: The spin state story: Observation of the quantum spin liquid state in novel material

New insight into the spin behavior in an exotic state of matter puts us closer to next-generation spintronic devices

Aside from the deep understanding of the natural world that quantum physics theory offers, scientists worldwide are working tirelessly to bring forth a...

Im Focus: Excitation of robust materials

Kiel physics team observed extremely fast electronic changes in real time in a special material class

In physics, they are currently the subject of intensive research; in electronics, they could enable completely new functions. So-called topological materials...

Im Focus: Electrons in the fast lane

Solar cells based on perovskite compounds could soon make electricity generation from sunlight even more efficient and cheaper. The laboratory efficiency of these perovskite solar cells already exceeds that of the well-known silicon solar cells. An international team led by Stefan Weber from the Max Planck Institute for Polymer Research (MPI-P) in Mainz has found microscopic structures in perovskite crystals that can guide the charge transport in the solar cell. Clever alignment of these "electron highways" could make perovskite solar cells even more powerful.

Solar cells convert sunlight into electricity. During this process, the electrons of the material inside the cell absorb the energy of the light....

Im Focus: The lightest electromagnetic shielding material in the world

Empa researchers have succeeded in applying aerogels to microelectronics: Aerogels based on cellulose nanofibers can effectively shield electromagnetic radiation over a wide frequency range – and they are unrivalled in terms of weight.

Electric motors and electronic devices generate electromagnetic fields that sometimes have to be shielded in order not to affect neighboring electronic...

Im Focus: Gentle wall contact – the right scenario for a fusion power plant

Quasi-continuous power exhaust developed as a wall-friendly method on ASDEX Upgrade

A promising operating mode for the plasma of a future power plant has been developed at the ASDEX Upgrade fusion device at Max Planck Institute for Plasma...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Contact Tracing Apps against COVID-19: German National Academy Leopoldina hosts international virtual panel discussion

07.07.2020 | Event News

International conference QuApps shows status quo of quantum technology

02.07.2020 | Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

 
Latest News

Porous graphene ribbons doped with nitrogen for electronics and quantum computing

09.07.2020 | Physics and Astronomy

Record efficiency for printed solar cells

09.07.2020 | Power and Electrical Engineering

Rock 'n' control

09.07.2020 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>