A recent study by the University of Bonn at least points in this direction. If the sensor fails, chronic inflammation may result — probably the beginning of a dangerous vicious circle. The publication appears in the journal Frontiers in Molecular Neuroscience.

The activity of the so-called microglial cells plays an important role in brain aging. These cells are part of the brain’s immune defense: For example, they detect and digest bacteria, but also eliminate diseased or defective nerve cells. They also use messenger substances to alert other defense cells and thus initiate a concerted campaign to protect the brain: an inflammation.

This protective mechanism has undesirable side effects; it can also cause damage to healthy brain tissue. Inflammations are therefore usually strictly controlled, Science Daily reported.

“We know that so-called endocannabinoids play an important role in this,” explains Dr. Andras Bilkei-Gorzo from the Institute of Molecular Psychiatry at the University of Bonn. “These are messenger substances produced by the body that act as a kind of brake signal: They prevent the inflammatory activity of the glial cells.”

Endocannabinoids develop their effect by binding to special receptors. There are two different types, called CB1 and CB2. “However, microglial cells have virtually no CB1 and very low level of CB2 receptors,” emphasizes Bilkei-Gorzo. “They are therefore deaf on the CB1 ear. And yet they react to the corresponding brake signals — why this is the case, has been puzzling so far.”

Neurons as “middlemen”

The scientists at the University of Bonn have now been able to shed light on this puzzle. Their findings indicate that the brake signals do not communicate directly with the glial cells, but via middlemen — a certain group of neurons, because this group has a large number of CB1 receptors. “We have studied laboratory mice in which the receptor in these neurons was switched off,” explains Bilkei-Gorzo. “The inflammatory activity of the microglial cells was permanently increased in these animals.”

In contrast, in control mice with functional CB1 receptors, the brain’s own defense forces were normally inactive. This only changed in the present of inflammatory stimulus. “Based on our results, we assume that CB1 receptors on neurons control the activity of microglial cells,” said Bilkei-Gorzo. “However, we cannot yet say whether this is also the case in humans.”

This is how it might work in mice: As soon as microglial cells detect a bacterial attack or neuronal damage, they switch to inflammation mode. They produce endocannabinoids, which activate the CB1 receptor of the neurons in their vicinity. This way, they inform the nerve cells about their presence and activity. The neurons may then be able to limit the immune response. The scientists were able to show that neurons similarly regulatory the other major glial cell type, the astroglial cells.

During ageing the production of cannabinoids declines reaching a low level in old individuals. This could lead to a kind of vicious circle, Bilkei-Gorzo suspects: “Since the neuronal CB1 receptors are no longer sufficiently activated, the glial cells are almost constantly in inflammatory mode. More regulatory neurons die as a result, so the immune response is less regulated and may become free-running.”

It may be possible to break this vicious circle with drugs in the future. It is for instance hoped that cannabis will help slow the progression of dementia. Its ingredient, tetrahydrocannabinol (THC), is a powerful CB1 receptor activator — even in low doses free from intoxicating effect. Last year, the researchers from Bonn and colleagues from Israel were able to demonstrate that cannabis can reverse the aging processes in the brains of mice. This result now suggest that an anti-inflammatory effect of THC may play a role in its positive effect on the ageing brain.

Led by Professor Alfonso Jaramillo in the School of Life Sciences, new research has discovered that a common molecule — ribonucleic acid (RNA), which is produced abundantly by humans, plants and animals — can be genetically engineered to allow scientists to program the actions of a cell.

As well as fighting disease and injury in humans, scientists could harness this technique to control plant cells and reverse environmental and agricultural issues, making plants more resilient to disease and pests.

RNAs carry information between protein and DNA in cells, and Professor Jaramillo has proved that these molecules can be produced and organised into tailor-made sequences of commands — similar to codes for computer software — which feed specific instructions into cells, programming them to do what we want.

Much like a classic Turing computer system, cells have the capacity to process and respond to instructions and codes inputted into their main system, argues Professor Jaramillo.

Similar to software running on a computer, or apps on a mobile device, many different RNA sequences could be created to empower cells with a ‘Virtual Machine’, able to interpret a universal RNA language, and to perform specific actions to address different diseases or problems.

This will allow a novel type of personalised and efficient healthcare, allowing us to ‘download’ a sequence of actions into cells, instructing them to execute complex decisions encoded in the RNA.

The researchers made their invention by first modelling all possible RNA sequence interactions on a computer, and then constructing the DNA encoding the optimal RNA designs, to be validated on bacteria cells in the laboratory.

After inducing the bacterial cells to produce the genetically engineered RNA sequences, the researchers observed that they had altered the gene expression of the cells according to the RNA program — demonstrating that cells can be programmed with pre-defined RNA commands, in the manner of a computer’s microprocessor.

Professor Alfonso Jaramillo, who is part of the Warwick Integrative Synthetic Biology Centre, commented:

“The capabilities of RNA molecules to interact in a predictable manner, and with alternative conformations, has allowed us to engineer networks of molecular switches that could be made to process arbitrary orders encoded in RNA.

“Throughout the last year, my group has been developing methodologies to enable RNA sensing the environment, perform arithmetic computations and control gene expression without relying on proteins, which makes the system universal across all living kingdoms.

“The cells could read the RNA ‘software’ to perform the encoded tasks, which could make the cells detect abnormal states, infections, or trigger developmental programs.”