Bodyguard for the brain

University of Bonn via EurekAlert ^ | 12-Jul-2011 | Dr. Andras Bilkei-Gorzo

[Pharmboy]

Researchers from the Universities of Bonn and Mainz discover a mechanism that can protect from aging processes

Humans are getting older and older, and the number of people with dementia is increasing. The factors controlling degeneration of the brain are still mostly unknown. However, researchers assume that factors such as stress, accumulation of toxic waste products as well as inflammation accelerate aging. But, vice versa, there are also mechanisms that can - like a bodyguard - protect the brain from degenerating, or repair defective structures.

Researchers from the Universities of Bonn and Mainz have now discovered a hitherto unknown function of the cannabinoid-1 receptor (CB1). A receptor is a protein that can bind to other substances, triggering a chain of signals. Cannabinoids such as THC – the active agent in cannabis sativa – and endocannabinoids formed by the body bind to the CB1 receptors. The existence of this receptor is also the reason for the intoxicating effect of hashish and marijuana.

Not only does the CB1 receptor have an addictive potential, but it also plays a role in the degeneration of the brain. "If we switch off the receptor using gene technology, mouse brains age much faster," said Önder Albayram, principal author of the publication and a doctoral student on the team of Professor Dr. Andreas Zimmer from the Institut für Molekulare Psychiatrie at the University of Bonn. "This means that the CB1 signal system has a protective effect for nerve cells."

Mice prove their brain power in a pool

The researchers studied mice in different age categories – young six week old animals, middle-aged ones at five months, and those of an advanced age at 12 months. The animals had to master various tasks – first, they had to find a submerged platform in the pool. Once the mice knew its location, the platform was moved, and the animals had to find it again. This was how the researchers tested how well the rodents learned and remembered.

The animals in which the CB1 receptor had been switched off (the knock-out mice) clearly differed from their kind. "The knock-out mice showed clearly diminished learning and memory capacity," said Privatdozent Dr. Andras Bilkei-Gorzo from Professor Zimmer's team, who led the study. So, animals that did not have the receptor were less successful in their search for the platform. "In addition, they showed a clear loss of nerve cells in the hippocampus," he explained further. This part of the brain is the central area for forming and storing information. In addition, the researchers found inflammation processes in the brain. As the mice advanced in age, the degenerative processes became increasingly noticeable.

Amazing parallels with the human brain

The animals with the intact CB1 receptor, to the contrary, did clearly better with regard to their learning and memory capabilities, as well as the health of their nerve cells. "The root cause of aging is one of the secrets of life," commented Albayram. This study has begun to open the door to solving this enigma. The processes in the mouse brains have a surprising number of parallels with age-related changes in human brains. So, the endocannabinoid system may also present a protective mechanism in the aging of the human brain.

The principal author cautioned, "This will require additional research." The scientists would like to better understand the mechanism by which CB1 receptors protect the brain from inflammation processes. And based on these signal chains, it might then be possible to develop substances for new therapies.

### Publication: Onder Albayram, Judith Alferink, Julika Pitsch, Anastasia Piyanova, Kim Neitzert, Karola Poppensieker, Daniela Mauer, Kerstin Michel, Anne Legler, Albert Becker, Krisztina Monory, Beat Lutz, Andreas Zimmer and Andras Bilkei-Gorzo: Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging, Proceedings of the National Academy of Sciences (PNAS), www.pnas.org/cgi/doi/10.1073/pnas.1016442108

Contact: Privatdozent Dr. Andras Bilkei-Gorzo Institut für Molekulare Psychiatrie der Universität Bonn Ph.: 0228/6885317 Email: abilkei@uni-bonn.de

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[Pharmboy]

OK, so lemme get this straight: people who smoke dope may see less neural degeneration because they keep their CB1 receptors stimulated. Soon to be in Obamacare, I presume...

[muawiyah]

No, those who use MJ should see MORE neural degeneration as their CB1 receptors become clogged with THC.

Much as many independent observers have noted.

At the same time the lead researcher advises us that "Zis vill require addishonal rezearch, uh hum." The scientists would like to better understand the mechanism by which CB1 receptors protect the brain from inflammation processes which will require a very large supply of clogging ingredients ~ uhh ~ you know, the usual kind ~ because those lab mice really need a lot.

[aruanan]

No, those who use MJ should see MORE neural degeneration as their CB1 receptors become clogged with THC.

It's a functional CB1 receptor binding to endogenously produced cannabinoids that is protective. A functional receptor binding to endogenous or exogenous cannabinoids is not equivalent to a blocked (clogged) or missing receptor. I say this from the point of view of someone whose four year postdoctoral fellowship was in neurobiology/pharmacology in neural cell signaling receptors.

[Marylander]

Perhaps the researchers can’t see the forest for the trees. It seems to me they have not only turned off the particular receptors, but also in the process, destroyed other parts of brain cells. Their conclusions may be nowhere near what may be justified by the experiment.

[muawiyah]

Still, for all your degrees the cold hard fact is this was JUST DISCOVERED and after your education.

You are just guessing as are we all. The original report here probably ends in a request for more money to continue the study ~ to see if those CB1 receptors can be OVERWHELMED ~ or CLOGGED ~ and those bad boys will need lots and lots of money (and a government license) to test THC night and day eh!

One thing I've found is that dopers tend to have no sense of humor ~ at their expense anyway.

[maica]

What is an endogenous cannabinoid? Do we all have them?

[Pharmboy]

No...aruanan is correct. This is not a receptor blocker but rather a stimulator of the CB1 receptor site. While I am only a physician and not a neuroscientist like aruanan, I did spend 3 years working on a CB1 receptor blocker that was being developed for obesity (it caused a bit of depression and is not used now).

So, theoretically, stimulation of the CB1 receptor by THC or other molecules might slow neural degeneration, but this is highly theoretical (but the basics as aruanan and I have said) are correct.

[Pharmboy]

Not likely, since they used “knock-out mice” which just affects the gene-product of what they knocked out (here, the CB1 receptor). It is a precision research technique often used to find out specific effects of various proteins in the body (or mouse body, to be exact).

[AFreeBird]

Okay, so how does one keep this receptor stimulated, active and healthy without getting stoned? Cause I don’t do that...

[Pharmboy]

Indeed we do. Most drugs work by mimicking natural substances made in the body. For example, beta blockers (used to treat various heart disease and hypertension) attach to the beta adrenergic receptors in the body; Valium and other so-called benzodiazepines attach to a receptor in the brain that modifies the chloride channel. Whenever a receptor (which is a protein) is discovered, we know that a natural substance must be present to activate, modify its activity or, at times, even block it.

The CB1 receptor was theorized for years, but cloned in the early '90s.

[Pharmboy]

GREAT question...in our bodies, we only produce small amounts of the natural substances that stimulate the CB1 receptor and then these substances are quickly metabolized and disappear. The CB1 receptor is one of the most common receptors in the brain. It is found in the so-called reward center of the brain, and is thought to be activated during sex and during eating. That is the theoretical reason for the "munchies" that marijuana users get. Click here for more info.

[Silentgypsy]

Ping

[decimon]

Ping

Thanks, Silentgypsy.

[redangus]

Does that mean rather than smoking dope we can get the same effect by having sex? Oh honey can you help me find my keys;.

[Pharmboy]

LMAO...I love the ingenuity of Freepers...

[Daffynition]

>>had to find a submerged platform in the pool. Once the mice knew its location, the platform was moved, and the animals had to find it again.<<

I'm still trying to wrap my mind around swimming mice...

Glad I have PETA on speed dial.

[Pharmboy]

Love it...but I would have thought a mouse would have little otters on his tube and not fish (being a mammal).

[Pharmboy]

Love it...but I would have thought a mouse would have little otters on his tube and not fish (being a mammal).

[aruanan]

Still, for all your degrees the cold hard fact is this was JUST DISCOVERED and after your education. You are just guessing as are we all. The original report here probably ends in a request for more money to continue the study ~ to see if those CB1 receptors can be OVERWHELMED ~ or CLOGGED ~ and those bad boys will need lots and lots of money (and a government license) to test THC night and day eh!

From the above we can see there is something that appears to be impairing your ability to reason: It is the relationship of functional CB1 receptors to maintaining neurological health that is the news item, not the basic physiology of receptors. I'm telling you something about how receptors are known to work. This means that if functional CB1 receptors are protective of mental acuity in older age it is because they are working as receptors and binding to their ligand, which is endogenously produced cannabinoids. The question of whether certain exogenously-supplied cannabinoids could supplement an age-linked reduction in endogenously-produced cannabinoids and maintain or improve mental acuity is still open. Given the toll on society and the misery experienced by those with various types of senility, it only makes sense to explore the possibilities. Refraining from this because some people smoke marijuana to get high is as absurd as claiming that we should rid our pharmacopia of all opioids because some Chinese junkies enjoyed smoking opium.

Your comments are truly humorous because whereas I talked about actual, known, receptor function and how that relates to a receptor's ligand, you posit a "probably" that details nothing more than a fantasy based on nothing more than what you want (or don't want) to be true.

maica: yes, the body produces cannabinoids just as it produces opioids. The reason the exogenous versions of these drugs have any effect at all is because they are able to dock with the receptors. There are substances that irreversibly bind to receptors and block their action such as bungarotoxin (from the Taiwanese krait) and epibatidine (from a poison arrow frog), which block the transmission of nerve impulses to muscles and cause death through asphyxiation. Additional amounts of the ligand, whether exogenously supplied THC or morphine, don't block the receptor; they stimulate it very, very well. In the case of morphine, the exogenous supply results in a down-regulation of the endogenous production, leading to extreme levels of pain if the exogenous form is discontinued too suddenly before the endogenous production can get ramped up. Another recent paper demonstrates that the interaction of cannabinoids with the CB1 receptor "suggest that locally produced endocannabinoids, acting via CB(1) play a role in mediating changes in permeability with inflammation, and that phytocannabinoids may possess therapeutic potential in reversing disordered intestinal permeability associated with inflammation." This is really interesting because of the role of inflammatory processes with age-related dementia.

[maica]

Thanks for the info. I am hitting the demographic where senility becomes more and more of a possibility. I don’t want to use up or clog my CB1 receptors if I can help it!