The discovery of a new signaling pathway in neurons could help researchers understand how to protect the brain during a stroke. Researchers have long thought that a protein called the NMDA receptor was principally responsible for neuron death during a stroke, but the new animal study shows that it is, in fact, the interaction between NMDA receptors and another protein known as pannexin-1, that causes the neurons to die. The discovery was made at the Hotchkiss Brain Institute (HBI) at the University of Calgary’s Cumming School of Medicine, and published this week in the journal Nature Neuroscience.
Neurons in the brain naturally release the neurotransmitter glutamate, but during a stroke they lose their ability to control how much is released. Too much glutamate overstimulates receptors and causes neurons to die, which is what can lead to disability in stroke survivors.
“The study provides a new framework to understand and target cell death in the brain and improve recovery after stroke,” says Roger Thompson, PhD, a researcher at the HBI assistant professor in the Department of Cell Biology and Anatomy. “This study will make a big impact in understanding brain physiology and pathology.”
Using this new information, researchers were able to develop and test a novel, small peptide therapeutic that disrupts the communication between the NMDA and pannexin-1 proteins. As part of the study, researchers had rats perform a skilled task following a stroke. After a few weeks of observations, the group who received the therapeutic were better able to perform the task, reaching for food, compared to the control group.
“The recovery from the stroke brought the animals back to normal because the drug protected the brain,” says Thompson. “The recovery wasn’t instant. This leads us to believe the drug protected the brain of the animal and reduced disability.”
“The results look promising,” says Nicholas Weilinger, PhD, the study’s first author. “We all know translation of a new drug takes time. Given the novelty of the compound itself, it is difficult to predict how long it will take for a drug like this to reach the clinic.”
The next steps of the study include further animal studies and toxicology testing, before potentially moving into clinical trials. Researchers who were part of the study believe this drug could one day be used in conjunction with other stroke therapies to improve stroke outcomes.
Scientists are very enthusiastic about this kind of research, which shows how the discovery of fundamental knowledge in brain signaling can lead to the development of novel drugs for stroke therapy and the potential for better patient outcomes.
The study was funded by the Canadian Institutes for Health Research (CIHR), and the Natural Sciences and Engineering Research Council of Canada (NSERC).
Source of text: University of Calgary
Original research article:
Weilinger NL, Lohman AW, Rakai BD, Ma EM, Bialecki J, Maslieieva V, Rilea T, Bandet MV, Ikuta NT, Scott L, Colicos MA, Teskey GC, Winship IR, Thompson RJ. Metabotropic NMDA receptor signaling couples Src family kinases to pannexin-1 during excitotoxicity. Nat Neurosci. 2016 Feb 8. doi: 10.1038/nn.4236.