Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Newly discovered mechanism controls levels and efficacy of a marijuana-like substance in the brain

09.08.2010
Therapies aimed at this and other cannabinoid signaling systems might help people with multiple sclerosis, Huntington's disease and other neurological disorders

A newly discovered molecular mechanism helps control the amount and effectiveness of a substance that mimics an active ingredient in marijuana, but that is produced by the body's own nerve cells.

The results were reported in the latest Nature Neuroscience. The lead author on the study is William R. Marrs of the Neurobiology and Behavior program at the University of Washington (UW). The senior author is Dr. Nephi Stella, UW professor of pharmacology and psychiatry.

In previous papers, Stella and other scientists have noted that the body manufactures several cell signals that mimic the actions of marijuana-derived chemicals These signals are called endocannabinoids, a Latin-derived name for marijuana-like (cannabis) constituents created by the body's own cells (endo).

Marrs, Stella and their research team study endocannabinoids, their receptors on cells, and the cell functions controlled by these signals.

They hope their future work encourages the design of therapies to modulate these molecular communications. Specifically targeted treatments, for example, might give cancer and AIDS patients the same medicinal benefits as marijuana without its mind-altering properties.

Because cannabinoid signaling systems are common throughout the body and affect a variety of functions, therapies aimed at these systems might be more wide-ranging than simply a better substitute for medicinal marijuana. Stella is especially interest in the potential for helping people with conditions for which even symptomatic treatment is limited or non-existent, such as multiple sclerosis, brain tumors, Huntington's disease and other autoimmune or neurological disorders.

Earlier Stella's group discovered a key endocannabinoid, called 2-AG, that carries a type of messaging between brain cells. 2-AG is also implicated in brain cell migration and brain tissue inflammation. It does this by activating one type of cannabinoid receptor on neurons, and another type of cannabinoid receptor on microglia, the tiny cells that clean up debris, like damaged nerve cells and plaque, in the brain and spinal cord. As the brain's first line of defense against infection, microglia are attune to the most subtle clues suggesting an attack.

Stella's team further investigated 2-AG nerve cell signaling in the study just published in Nature Neuroscience. They looked at an enzyme called ABHD6, newly identified by other scientists using advanced protein profiling technology, also known as proteomics. ABHD6 is present in nerve cells in the brain.

Stella's team observed that this enzyme degrades the 2-AG nerve signaling substance by splitting it with water. This happens near the cell receptor for the 2-AG signal.

Breaking apart 2-AG reduced its accumulation and decreased its ability to prod other cells to action. In this case, the broken down 2-AG was less effective in stimulating the microglia – the brain defenders -- to get moving.

The results provided by their study, the authors said, suggest that the enzyme ABDH6 "is a bona fide member of the endocannabinoid signaling system."

"The enzymatic steps that control the production and inactivation of endocannabinoids constitute promising molecular targets for indirectly modulating the activity of cannabinoid receptors," the authors noted. Designing treatments that manage the production and inactivation of important enzymes like ABHD6 could thereby control such conditions as brain inflammation or overactive brain signals. Other enzymes are involved in controlling the accumulation of different endocannabinoids.

Each of these enzymes, the researchers pointed out, provides a unique therapeutic opportunity. Inhibiting distinct enzymes would allow for the fine-tuned direction of endocannabinoid signaling. For example, blocking a specific enzyme to heighten a certain signal might ameliorate pain and also act as anti-anxiety and antidepressant therapy, the authors explained. Drugs that reduce the activity of the ABDH6 enzyme might prevent brain damage from an overactive response to a virus.

The study was supported by grants from the National Institute on Drug Abuse and the National Institute of General Medical Sciences, both part of the National Institutes of Health.

In addition to Marrs and Stella, other researchers on the study are Jacqueline L. Blankman, Jessica P. Alexander, Jonathan Z. Long, Weiwei Li, and Benjamin F. Cravatt, all of Scripps Research Institute; Eric A. Horne, Yi Hsing Lin, Jonathan Coy, and Cong Xu, all of the UW Department of Pharmacology; Aurore Thomazeau, Mathieu LaFourcade and Olivier J. Manzoni, all of INSERM, Bordeaux, France; Agnes L. Bodor of the UW Department of Otolaryngology; Giulio G. Muccioli of the Louvain Drug Research Institute, Bruxelles, Belgium; Sherry Shu-Jung Hu and Ken Mackie, of Indiana University; Grace Woodruff of the UW Neurobiology Undergraduate Program; Susan Fung of the UW Neurobiology and Behavior Graduate Program, and Thomas Moller of the UW Department of Neurology.

Leila Gray | EurekAlert!
Further information:
http://www.washington.edu

More articles from Life Sciences:

nachricht Making fuel out of thick air
08.12.2017 | DOE/Argonne National Laboratory

nachricht ‘Spying’ on the hidden geometry of complex networks through machine intelligence
08.12.2017 | Technische Universität Dresden

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

Im Focus: Virtual Reality for Bacteria

An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications

Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...

Im Focus: A space-time sensor for light-matter interactions

Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.

The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

Blockchain is becoming more important in the energy market

05.12.2017 | Event News

 
Latest News

New research identifies how 3-D printed metals can be both strong and ductile

11.12.2017 | Physics and Astronomy

Scientists channel graphene to understand filtration and ion transport into cells

11.12.2017 | Materials Sciences

What makes corals sick?

11.12.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>