Researchers at the University of Göttingen have studied what happens when certain enzymes are blocked in mice and depending on whether the brain is healthy or diseased, the inhibition has opposite effects. The research has been published in the ‘Journal of Neuroscience’.
Learning and recovery from injury depends on the plasticity of neural connections. The macromolecules of the extracellular matrix, located between the nerve cells, are important for this. As we grow older, the “stability” of this extracellular matrix increases, providing a scaffold to stabilize existing connections between nerve cells and consolidate what we have learned. If we are experiencing something new, the extracellular matrix must be released to allow new connections to form. This relationship between stability and plasticity in the brain is regulated in the matrix with the help of enzymes such as matrix metalloproteinases (MMPs), which can “digest” the extracellular matrix and thus “loosen” it. A team from the University of Göttingen has just shown in a new study that blocking the matrix metalloproteinases MMP2 and MMP9 can have opposite effects depending on whether the brain is sick or healthy.
To measure neuronal plasticity, the scientists let adult mice see through one eye for several days and recorded the resulting changes in activity in the animals’ visual cortex. In a first experiment, they examined the adaptability of the visual cortex of healthy mice in which the MMP2 and MMP9 enzymes were blocked (with SB3CT). As a result, neuronal plasticity was also blocked. In a second experiment, the team looked for mice immediately after a stroke. It was already known that a stroke leads to a sharp short-term increase in MMPs. In this case, the targeted and short-term inhibition of the MMP2 and MMP9 enzymes produced the opposite effect: the plasticity which had been greatly reduced by the stroke was restored, so that the blockage of the MMP2 and MMP9 enzymes was restored. had a clear therapeutic effect.
“What made the design of our study different from many previous studies is that the ‘matrix degrading’ enzymes were only blocked after the experimental stroke, which mimics the treatment,” said the Professor Siegrid Lowel of the Department of Systems Neuroscience at the University of Göttingen. “We also show that MMPs in the brain need to be very well monitored and fine-tuned. Too low in healthy brain prevents neuronal plasticity and too high – like after a stroke – also blocks neural plasticity. “. Lowel added. (ANI)
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