 |
|
|
Stress response in the brain relies on a blood-thinning protein
November 19, 2007
A stressed-out mouse tends to be a bit timid, tentative, even fearful. For that
matter, so does a stressed-out human. Our ability to learn from frightening
situations is part of what helps us avoid them in the future. When that learning
process goes awry, it can lead to depression and a decreased ability to
recognize dangerous situations. Now, research by Rockefeller scientists has
pinned down a protein in the hippocampus — a part of the brain that controls
memory, learning and fear — that’s essential for maintaining this stress
response.
The protein tPA (tissue plasminogen activator) is best known for its ability to
dissolve blood clots. But more and more studies are showing that it also plays a
role in neural plasticity in the brain. Sidney Strickland, head of the
Laboratory of Neurobiology and Genetics, and postdoc Erin Norris have taken the
research a step further to see whether tPA has anything to do with how stress
affects memory, learning ability and anxiety.
Prior research from the Strickland lab had shown that mice lacking tPA also seem
to lack fear, a behavior largely dictated by a part of the brain called the
amygdala. To determine whether tPA also affects behavior controlled by the
hippocampus, Norris and Strickland compared normal mice to tPA-deficient ones.
Then they divvied the mice up further: Half of each group they left alone, and
the rest they exposed to six hours of painless restraint stress. Once the groups
were complete, the researchers placed each mouse — wild-type, stressed
wild-type, tPA-deficient and stressed tPA-deficient — into a small chamber,
where the rodents were exposed to a sound paired with a small electric shock.
The next day they returned the mice to the chamber, but this time left them
alone.
All of the non-stressed as well as the stressed wild-type mice appeared to have
learned from experience, showing their fear of the chamber in the form of
freezing behavior. In comparison, the mice lacking tPA had significantly reduced
freezing responses. “So they were either less fearful of their situation, or
they just didn’t remember — they didn’t learn from their training,” Norris says.
“We could say that if you don’t have tPA and you are in a stressful situation,
you don’t have synaptic plasticity changes in the hippocampus.” The wild-type
mice were capable of learning because tPA could induce changes in their brains’
neural synapses.
Norris and Strickland believe that the underlying mechanism for this has to do
with a receptor that normally resides at the cell membrane but changes its
location during stress. They found that, in mice lacking tPA, the receptor
stayed anchored at the membrane even during stress. And without the receptor’s
change in position, there could be no stress response. Norris has since begun
investigating whether tPA could also be an important factor in depression, since
stress has been shown to lead to this disorder in humans.
Proceedings of the National Academy of Sciences 104(33): 13473–13478 (August 14,
2007)
Laboratory of Neurobiology and Genetics
Contact: Lauren Gravitz 212-327-8977
newswire@rockefeller.edu
| |
