Nature: New uses for old medicines! New research reveals the molecular mechanisms of ketamine against depression

DECEMBER 20, 2020 /--- In a new study, researchers from McGill University, the University of Montreal and the University of Carlton in Canada found that a group of proteins involved in memory formation called 4E-BP is key to unlocking ketamine antidepressants in the brain.
findings could lead to better and safer treatments for some people with severe depression.
results were published online December 16, 2020 in the journal Nature under the title "Antidepressant actions of ketamine engage cell-specific via if4E".
images from Nature, 2020, 10.1038/s41586-020-03047-0.
Finding effective treatments for severe depression is a challenge, given that more than 30--- percent of patients develop resistance to the most commonly used antidepressant, selective serotonin reuptake inhibitor (SSRI) ---.
, ketamine was approved for anaesthetic and pain relief.
scientists have been studying new uses for the drug since its discovery, and last year ketamine was approved for use in the treatment of patients with severe depression who are resistant to drugs.
antidepressants, which can take weeks to produce results, ketamine can work in a matter of hours.
so far, little is known about the molecular mechanisms by which ketamine has antidepressants in the brain.
the new study, the researchers looked at the effects of ketamine on mouse behavior and neuronal activity.
they used genetic tools to remove proteins from specific brain cells and found that ketamine did not produce antidepressants when the brain, especially neurons, lacked 4E-BP protein.
4E-BP is like a switch that turns protein synthesis on or off--- an important part of memory formation. "This is another classic example of basic research that refers to control of protein synthesis, how it leads to major discoveries of disease, and potential cures for disease," said Nahum Sonenberg, co-author of the
paper and a professor in the Department of Biochemistry at McGill University.
" researchers studied the role of 4E-BP in two main types of neurons: excitable neurons, which make up the majority of neurons in certain parts of the brain, and inhibitors, which control excitable neurons, which have important effects on behavior. "We thought 4E-BP would only play an important role in excitable cells, but surprisingly, removing 4E-BP from inhibitory cells is enough to block ketamine," said Jean-Claude Lacaille, co-author of the
paper and a professor in the Department of Neuroscience at the University of Montreal.
"the absence of drugs for all and the approval of ketamine for the treatment of drug-resistant patients is considered a major advance in modern psychiatry."
promising, ketamine is still an imperfect treatment because it can be addictive.
the researchers hope their findings could pave the way for better and safer antidepressant therapies for people with severe depression.
decisions are still made by trial and error, which can prolong patients' pain and affect their quality of life," said Argel Aguilar-Valles, co-author of the paper and lead author of the paper.
our findings have the potential to bring us closer to finding a safer alternative to ketamine and ultimately to personalize treatments that are tailored to each patient's individual characteristics.
study also involved a clinician researcher, Dr Gabriela Gobbi of McGill University's Department of Psychiatry.
Gobbi study looked at people affected by depression and other mental illnesses.
as a next step, the researchers will study whether men and women react differently to ketamine.
this may have a significant impact on the treatment of people with depression, after all, the proportion of women in patients with depression is significantly higher.
(Bioon.com) Reference: 1. Argel Aguilar-Valles et al. Antidepressant actions of ketamine engage cell-specific translation via eIF4E. Nature, 2020, 10.1038/s41586-020-03047-0.2.New use for an old drug: How does ketamine combat depression?