Mice provide many important clues to the obsessive-compulsive disorder

Danh Phuong

The mice born without key brain proteins were like being forced to rub their faces until they bleed and were afraid to dare to get out of the corner. When offered an alternative protein dose to a specific area of ​​the brain, or the drug is used to treat people who are suffering from obsessive-compulsive disorder (obsessive-compulsive disorder - abbreviated as OCD). ), many of these mice become better.

Investigators from Duke University Medical Center, in a basic study of how to combine individual brain cells with each other, were fortunate to discover mice with genetic mutations. preventing their brain cells from producing a key protein, which has shown to act like OCD.

The discovery seems to have exposed important clues to a possible technique for OCD, a neurodegenerative condition that affects more than 2% of the world's population.

The international team of researchers led by Duke molecular geneticist Dr. Guoping Feng reported this finding in the August 23 issue of Nature . The study was supported by the National Institutes of Health, McKnight Neuroscience Science Foundation, and Hartwell Foundation.

Mice that were anesthetized with SAPAP3 protein had a scratched patch of skin that was bleeding from the face due to self-waving action.(Photo: Dr. Guoping Feng, Duke University)

"The mice that were unable to produce proteins showed a similar action to those in people with OCD, a mandatory action associated with increased anxiety," Feng said . Obviously, we can't talk to mice to know what they are thinking, but these mutant mice obviously do what looks like ODC. '

OCD is one of the most common mental disorders in the world. It is manifested by continuous intrusions (obsession), repetitive actions (compulsion) and anxiety. Strict disease OCD varies widely from person to person, and while the underlying neurological disease is unknown, there are some signs that genetics play a very important role. .

In their experiments, the Duke team focused on studying a part of the brain known as a striatum, which is an area of ​​predictive and destructive action, as well as cognitive function. other. It is a ' decision maker ' in many ways. In the normal brain, a protein known as SAPAP3 , is essential for nerve signals to travel from one neuron to another, passing through the synapse, the space between cells.

Feng explained: 'This protein is very important, helping messages pass through synapses, and it is produced at very high levels in cells that form striatum. When we looked at the close-up of brain cells in these mutant mice, we discovered that in synapses there are drawbacks in them. '

'When we went back to observing the protein inside the striatum of the brain in mutant mice, the weakness in the synapse was corrected and the actions like OCD were also eased.' Feng continued, 'This is the first direct evidence that the disadvantage of synapses in the striatum has caused actions like this ODC.'

The researchers also found a group of drugs known as selective serotonin reuptake inhibitors (SSRIs) that reduce anxiety levels and block excessive self-stirring action. The mice mutated , suggesting that more of what they observed in mice may be similar to human OCD. Serotonin, like SAPAP3, is one of many neurotransmitters, a chemical involved in the transmission of information in nerve cells.

While SSRI inhibitors are the most commonly prescribed drug for people with OCD, they are only effective for about half of the patients, which tells Feng there are many nerve bundles including Other neurotransmitters are very likely to be related to each other.

Feng and his colleague at Duke are now trying to find out more about genetic changes, which can affect the way nerves transmit signals through synapses, and they are also beginning to do research to decide. plan to see if the mutated gene they have detected in a mouse has a role in people with OCD.

To carry out this study, Feng collaborated with William Wetsel and Nicole Calakos from Duke University; Richard Weinberg from the University of North Carolina at Chapel Hill; Serena Dudek is from the National Institute of Environmental Health Sciences; as well as researchers from China Medical University; Coimbra University, Portugal; and Gulbenkian Science Institute, Portugal.

Note: This report is adapted from a news release published by Duke University Medical Center.