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New 'Stress Response' Chemical Pathway discovered

Messages
5,238
Location
Sofa, UK
Although the relevance of stress and depression issues to ME/CFS is of course controversial, any breakthrough in understanding them has to be a good thing, for us also since it should make it easier to distinguish those issues when they are present...


Neuroscientists Discover New 'Chemical Pathway' In The Brain For Stress

http://www.medicalnewstoday.com/articles/222991.php

A team of neuroscientists at the University of Leicester, UK, in collaboration with researchers from Poland and Japan, has announced a breakthrough in the understanding of the 'brain chemistry' that triggers our response to highly stressful and traumatic events.

The discovery of a critical and previously unknown pathway in the brain that is linked to our response to stress is announced today in the journal Nature. The advance offers new hope for targeted treatment, or even prevention, of stress-related psychiatric disorders.

About 20% of the population experience some form of anxiety disorder at least once in their lives. The cumulative lifetime prevalence of all stress-related disorders is difficult to estimate but is probably higher than 30%.

Dr Robert Pawlak, from the University of Leicester who led the UK team, said: "Stress-related disorders affect a large percentage of the population and generate an enormous personal, social and economic impact. It was previously known that certain individuals are more susceptible to detrimental effects of stress than others. Although the majority of us experience traumatic events, only some develop stress-associated psychiatric disorders such as depression, anxiety or posttraumatic stress disorder. The reasons for this were not clear."

Dr Pawlak added that a lack of correspondence between the commonness of exposure to psychological trauma and the development of pathological anxiety prompted the researchers to look for factors that may make some individuals more vulnerable to stress than others.

"We asked: What is the molecular basis of anxiety in response to noxious stimuli? How are stress-related environmental signals translated into proper behavioural responses? To investigate these problems we used a combination of genetic, molecular, electrophysiological and behavioural approaches. This resulted in the discovery of a critical, previously unknown pathway mediating anxiety in response to stress."

The study found that the emotional centre of the brain - the amygdala - reacts to stress by increasing production of a protein called neuropsin. This triggers a series of chemical events which in turn cause the amygdala to increase its activity. As a consequence, a gene is turned on that determines the stress response at a cellular level.

"We then examined behavioural consequences of the above series of cellular events caused by stress in the amygdala," said Dr Pawlak. "Studies in mice revealed that upon feeling stressed, they stayed away from zones in a maze where they felt unsafe. These were open and illuminated spaces they avoid when they are anxious."

"However when the proteins produced by the amygdala were blocked - either pharmacologically or by gene therapy - the mice did not exhibit the same traits. The behavioural consequences of stress were no longer present. We conclude that the activity of neuropsin and its partners may determine vulnerability to stress."

...

Dr Pawlak added: "We are tremendously excited about these findings. We know that all members of the neuropsin pathway are present in the human brain. They may play a similar role in humans and further research will be necessary to examine the potential of intervention therapies for controlling stress-induced behaviours."

"Although research is now needed to translate our findings to the clinical situation, our discovery opens new possibilities for prevention and treatment of stress-related psychiatric disorders such as depression and posttraumatic stress disorder."

"Neuropsin cleaves EphB2 in the amygdala to control anxiety"
Benjamin Attwood1, Julie-Myrtille Bourgognon1, Satyam Patel1, Mariusz Mucha1, Emanuele Schiavon1, Anna E. Skrzypiec1, Kenneth W. Young2, Sadao Shiosaka3, Michal Korostynski4, Marcin Piechota4, Ryszard Przewlocki4, Robert Pawlak1
Nature DOI: 10.1038/nature09938
 
Messages
5,238
Location
Sofa, UK
Here's the paper itself...note to self: must get into the habit of posting that rather than the press reports:
http://www.ncbi.nlm.nih.gov/pubmed/21508957

A minority of individuals experiencing traumatic events develop anxiety disorders. The reason for the lack of correspondence between the prevalence of exposure to psychological trauma and the development of anxiety is unknown. Extracellular proteolysis contributes to fear-associated responses by facilitating neuronal plasticity at the neuron-matrix interface. Here we show in mice that the serine protease neuropsin is critical for stress-related plasticity in the amygdala by regulating the dynamics of the EphB2-NMDA-receptor interaction, the expression of Fkbp5 and anxiety-like behaviour. Stress results in neuropsin-dependent cleavage of EphB2 in the amygdala causing dissociation of EphB2 from the NR1 subunit of the NMDA receptor and promoting membrane turnover of EphB2 receptors. Dynamic EphB2-NR1 interaction enhances NMDA receptor current, induces Fkbp5 gene expression and enhances behavioural signatures of anxiety. On stress, neuropsin-deficient mice do not show EphB2 cleavage and its dissociation from NR1 resulting in a static EphB2-NR1 interaction, attenuated induction of the Fkbp5 gene and low anxiety. The behavioural response to stress can be restored by intra-amygdala injection of neuropsin into neuropsin-deficient mice and disrupted by the injection of either anti-EphB2 antibodies or silencing the Fkbp5 gene in the amygdala of wild-type mice. Our findings establish a novel neuronal pathway linking stress-induced proteolysis of EphB2 in the amygdala to anxiety.

My interpretation is that they are not claiming to have discovered neuropsin and the known connection with stress/anxiety response - I am assuming that if the paper means anything like what the press spin is saying then it must be saying that they have uncovered the fundamental details of the neuronal pathway - basically, they've filled out the details on how this response works:

by regulating the dynamics of the EphB2-NMDA-receptor interaction, the expression of Fkbp5 and anxiety-like behaviour. Stress results in neuropsin-dependent cleavage of EphB2 in the amygdala causing dissociation of EphB2 from the NR1 subunit of the NMDA receptor and promoting membrane turnover of EphB2 receptors. Dynamic EphB2-NR1 interaction enhances NMDA receptor current, induces Fkbp5 gene expression and enhances behavioural signatures of anxiety. On stress, neuropsin-deficient mice do not show EphB2 cleavage and its dissociation from NR1 resulting in a static EphB2-NR1 interaction, attenuated induction of the Fkbp5 gene and low anxiety.
 
Messages
5,238
Location
Sofa, UK
I don't think this thread should be in:
Forum: Latest Research
Post links to news articles, abstracts, etc about PUBLISHED RESEARCH SPECIFIC TO ME/CFS.

Sorry...that's where I meant to put it and where I thought I had put it...rushing a bit today...sorry...
 

anne_likes_red

Senior Member
Messages
1,103
My interpretation is that they are not claiming to have discovered neuropsin and the known connection with stress/anxiety response - I am assuming that if the paper means anything like what the press spin is saying then it must be saying that they have uncovered the fundamental details of the neuronal pathway - basically, they've filled out the details on how this response works:

That was my interpretation too.

Thanks for posting Mark. V. interesting :)