Stress weakens link between neurons

For the first time, researchers verified the role the cell adhesion molecule nectin-3 plays in stress-related learning and memory deficits and showed a possible treatment strategy by inversion of the mechanism

May 07, 2013

The strength and number of synapses are essential for the function of the brain. Researchers around Mathias Schmidt from the Max Planck Institute of Psychiatry have now succeeded in demonstrating that the quantity of nectin-3, which contributes to the stabilization of synaptic contacts between neurons, is reduced by stress in early childhood. In the long run, lower nectin-3 levels lead to cognitive deficits. By artificially replenishing nectin-3, the researchers were able to repair these stress-induced changes in the neurons and to compensate for the deficits in learning and memory going along with them. This opens up new treatment approaches for stress-induced psychiatric diseases, such as depression.

One out of many nectin-3 expressing CA-3 neurons in the hippocampus.

“So far, it was known that stress can have negative effects on cognitive performance, especially on our memory,” explains Mathias Schmidt, head of the study. “Now we were able to identify nectin-3 as a key protein that determines the effects of stress on the quality and quantity of neuronal connections.”

Nectin-3 is one of several so-called cell adhesion molecules connecting cells. Within the brain, it is predominantly located at synapses and peri-synaptic sites, the junctions between different nerve cells. With regard to nectin-3, the researchers were interested in whether its expression is regulated by the well-known stress mediator corticotropin-releasing hormone (CRH), and in which way it modulates learning and memory capacity.

By comparing brain metabolism and behavior of genetically modified and normal mice, the researchers were able to show that animals with cognitive deficits and increased production of CRH had less nectin-3 in the hippocampus, a region essential for memory. This led to a significant loss of nerve cell contacts, which was accompanied by memory impairments.

As Mathias Schmidt explains, “The importance of the neuropeptide CRH for the regulation of stress effects has already been described in detail in earlier studies. The present results confirm this assessment and, as exemplified by nectin-3, show a new level through which CRH influences our brain functions.”

The work of the scientists is of particular importance, given that they were able to reverse the negative effects early life stress had caused. By specific over-expression of nectin-3 in the hippocampus, they could completely compensate for the stress-induced loss of nerve cell contacts – and thus for learning capacity.

“The question now is whether it will be possible to develop drugs that reinforce the production of nectin-3 in a targeted manner and thus enable a new treatment approach for various psychiatric disorders, such as depression,” Mathias Schmidt comments.

MG/BA

Go to Editor View