Stress code in the spotlight
Researchers at the University of Leicester in the United Kingdom have identified a specific protein generated by the brain in response to stress. Their findings, published in the journal Proceedings of the National Academy of Sciences (PNAS), could help boost our understanding of stress-related psychiatric diseases in people, particularly in knowing how the human brain deals with stress and how it eases its impact. The study was funded in part by a Marie Curie Excellence Grant under the EU's Seventh Framework Programme (FP7).
Scientists from Leicester's Department of Cell Physiology and Pharmacology investigated 'thin' and 'mushroom-like' parts of nerve cells in the brain that play a critical role in our learning and remembering processes. According to the researchers, people can tweak what they remember, thus mitigating the stress of painful memories.
Discovering the production of this specific protein in the brain that could help protect people from 'too much anxiety' and give organisms the help they need to deal with negative life events is a groundbreaking result of the study.
'Every day stress 'reshapes' the brain — nerve cells change their morphology, the number of connections with other cells and the way they communicate with other neurons,' explains Dr Robert Pawlak, a Neuroscience lecturer at the University of Leicester and one of the authors of the study. 'In most cases these responses are adaptive and beneficial — they help the brain to cope with stress and shape adequate behavioural reaction.'
But Dr Pawlak goes on to say that when severe stress emerges, 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,' he adds.
'One strategy that brain cells particularly like to use to cope with stress is changing the shape of tiny processes they normally employ to exchange information with other neurons, called dendritic spines.'
The size of spines can be as tiny as 1/1 000th of a millimetre; their shapes vary as well. The researchers compared long spines, what experts call 'thin' spines, in the case of children; not only are these spines mobile but they are also inquisitive. These spines change shape frequently and play a key role in our learning processes. When the spines learn, they mature, become mushroom-shaped and have stable connections. Not only do they not change partners, but they like to stay put as well.
'Mushroom spines help us remember things we once learned but it is not always good,' Dr Pawlak points out. '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,' he adds.
'We have 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. When we added lipocalin-2 to neurons in culture the way it occurs on stress, neurons started losing their 'memory spines' -- the mature, mushroom-shaped ones. 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.'
More than a third of the human population is affected by stress-related psychological and mental disturbances, according to the researchers. Their next plan of action is to determine whether the mechanisms they identified can be used to inform clinical strategies to manage anxiety disorders and depression.