Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Blocking enzyme found to ease anxiety without causing sedation


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:

More articles from Health and Medicine:

nachricht NIH scientists describe potential antibody treatment for multidrug-resistant K. pneumoniae
14.03.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht Researchers identify key step in viral replication
13.03.2018 | University of Pittsburgh Schools of the Health Sciences

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: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

Im Focus: Radar for navigation support from autonomous flying drones

At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.

Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

International Virtual Reality Conference “IEEE VR 2018” comes to Reutlingen, Germany

08.03.2018 | Event News

Latest News

Wandering greenhouse gas

16.03.2018 | Earth Sciences

'Frequency combs' ID chemicals within the mid-infrared spectral region

16.03.2018 | Physics and Astronomy

Biologists unravel another mystery of what makes DNA go 'loopy'

16.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>