Researchers at the University of Bonn have examined how quickly the brain ages in mice if a certain receptor is missing. Photo: University of Bonn |
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.
Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging
