A team of researchers from the University of Michigan and Johns Hopkins University have identified a protein in the brain that contributes to the sensation of coldness in mammals.
Shawn Xu, U-M professor in the Life Sciences Institute and the MIP department in the medical school, together with his collaborator Bo Duan, MCDB associate professor, discovered that the GluK2 protein is responsible for the feeling that accompanies cold exposure, and recently published their findings in Nature Neuroscience. Elizabeth Ronan, a former graduate student in Xu’s lab, said the higher goal of the lab is to investigate sensory systems.
“One significant research focus in the lab in recent years has been understanding how animals sense cold temperatures,” Ronan said. “While it’s well-established that mammals detect moderate cool temperatures through the sensory receptor ion channel TRPM8 — also activated by menthol to evoke a cooling sensation — much less is known about how animals sense noxious cold.”
Research on the mechanism behind cold temperature sensing has been ongoing for more than 20 years after the discovery of TRPV1, which is responsible for the detection and regulation of body temperature, specifically the sensation of heat. Gluk2 is coded for by the Grik2 gene, which is typically found on neurons in the brain. The researchers studied mice both with and without the Grik2 gene to identify if it played a role in temperature sensation. The mice were exposed to temperatures through the placement of temperature-controlled droplets placed on their hind paws.
Wenwen Zhang, a postdoctoral fellow at the Xu Lab, said observing mouse behavior was a key component of the experiment. According to Zhang, mice only have a behavior response to temperatures that are considered cold, less than 15 degrees Celsius, or hot, more than 42 degrees Celsius, and do not exhibit such responses to warm or cool temperatures between the extremes.
“When mices’ forepaws or hind paws are stimulated with noxious cold or hot temperature, they will have a series of reflex or self-caring reactions like lifting, flinching, licking, or even guarding their paws,” Zhang said.
It was ultimately discovered that the mice who did not have the GluK2 gene reacted to hot, warm and cool temperatures, but lacked reaction when exposed to the noxious cold temperatures.
Mahar Fatima, a former postdoctoral fellow in Duan’s lab, said she hopes the findings of this study bring advancements in the medical field.
“Currently, there are no effective drug therapies to encounter cold temperature-evoked pain observed in patients suffering from chronic pain,” Fatima said. “This study highlights GluK2 as an ideal drug target for developing clinical intervention for the patients suffering from heightened sensitivity to colder temperature.”
Daily Staff Reporter Chiara Dettin can be reached at chiarald@umich.edu.
Correction 3/22: A previous version of this article did not mention the contributions of Bo Duan. The article also incorrectly stated that Elizabeth Ronan is a current graduate student and that Mahar Fatima is a research laboratory specialist in Xu’s lab; Ronan is a former graduate student and Fatima is a postdoctoral fellow in Duan’s lab. A previous version of this article erroneously stated that the Gluk2 gene codes for the Gluk2 protein; the Grik2 gene codes for the Gluk2 protein. In addition, an earlier version of this article stated that the work was published in Nature. The research was published in Nature Neuroscience. This article has been updated to reflect these changes.
Correction 3/25: A previous version of this article incorrectly stated that Elizabeth Ronan is a Rackham student. The article has been updated to reflect the fact that she is a former graduate student.