Researchers from the University of Leicester have identified a particular protein that the brain produces in response to stress, an important step forward in understanding molecular mechanisms of anxiety.
The findings, published in Proceedings of the National Academy of Sciences (PNAS), are potentially important for understanding stress-related psychiatric diseases in humans.
Neuroscientist Robert Pawlak, M.D., Ph.D., said the study had determined that production of the protein by the brain may help to protect individuals from “too much anxiety” and help organisms to cope with various adverse life events.
Pawlak believes that everyday stress “reshapes” the brain – nerve cells change their morphology, the number of connections with other cells and the way they communicate with other neurons. And, in most cases these responses are adaptive and beneficial – they help us to cope with stress and shape adequate behavioral reaction.
“However, upon severe stress things can get out of control, the brain ‘buffering’ capacity is exhausted and the nerve cells in the hippocampus – an area of the brain responsible for learning and memory – start to withdraw their processes, don’t effectively communicate with other cells and show signs of disease,” Pawlak said.
In response to stress, neurons often change the shape of tiny structures they normally use to exchange information with other neurons, called dendritic spines. Spines can be as small as 1/1000 of a millimeter and have various shapes.
“Long spines (called ‘thin’ spines) are like children – very mobile and inquisitive, constantly change shape and ‘conversation’ partners – they help us learn new things,” Pawlak said. ”Once spines learn, they change into mature ‘couch potatoes’ – they are mushroom-shaped, have stable connections, do not change partners and do not like to move.”
“Mushroom spines help us remember things we once learned – but it is not always good. Some very stressful events would better be forgotten quickly or they may result in anxiety disorders. There is a constant battle of forces in our brain to help maintain the right balance of thin and mushroom spines – or how much to remember and what better to forget.”
In the new study, researchers identified a protein that the brain produces in response to stress in order to reduce the number of mushroom spines and therefore reduce future anxiety associated with stressful events.
This protein, lipocalin-2, is normally not produced, but its fabrication dramatically increases in response to stress in the hippocampus.
Researchers then decided to remove the protein (lipocalin-2) from the brain and subject mice to stress – watching how the mice would react. The experts found that when stressed, the mice with the absent protein were more anxious than normal mice.
For example, they were less “outgoing” and preferred hiding in dark, enclosed spaces instead of exploring the neighborhood normally. In these mice, mushroom spines were more readily formed in the brain after stress and they had stronger memories of the stressful event.
“Thus, the brain produces lipocalin-2 in order to protect us from ‘too much anxiety’ and help us cope with various adverse life events,” said Pawlak.
“Identification of lipocalin-2 as a new player the brain uses to help us cope with stress is an important step forward. We are getting closer to deciphering molecular mechanisms of stress that, if not functioning properly, may lead to stress-related psychiatric diseases”.
Since stress-related issues affect more than 30 percent of the population, the finding of physiological mechanisms that form in response to stress will help researchers develop clinical strategies to deal with anxiety and depression.
Source: University of Leicester