MUNICH (Dispatches) -- According to a new study, Ketamine, a well-known anesthetic, has paved its way toward the development of safe, effective treatments for depression.
As researchers at the Weizmann Institute of Science in Rehovot, and at the Max Planck Institute of Psychiatry in Munich, Germany, in collaboration with the Helmholtz Zentrum, Munich, tried to clarify ketamine’s mechanism of action in previous studies, they examined its impact on gene expression in brain tissues, but not in individual brain cells. This approach can miss crucial differences between different cell types. Recent technological advances, however, have made it possible to assess gene expression at an unprecedented level of resolution: that of the single cell. These technologies were employed in the new study, conducted under the guidance of Prof. Alon Chen, former managing director of the Max Planck Institute of Psychiatry and current president of the Weizmann Institute of Science.
Scientists mapped out gene expression in thousands of individual neurons in the brains of mice that had been given a dose of ketamine in this study.These neurons belong to networks that convey their signals by means of the neurotransmitter glutamate. Ketamine had been known since the 1990s to produce its effects by acting on such neurons -- this in contrast to older antidepressants, which mainly affect neurons influenced by serotonin. But since ketamine’s effect persists long after it leaves the body, its action could not be explained by mere blockage of glutamate receptors on the surfaces of neurons. They wanted to clarify the molecular cascade that is triggered by ketamine, leading to its sustained antidepressant effects.
The researchers focused on the ventral hippocampus, a brain region that in previous studies had been associated with the antidepressant effects of ketamine. After mapping out gene expression in cells from this area of the mouse brain. They identified a subpopulation of neurons with a characteristic genetic signature. Ketamine had increased these neurons’ expression of a gene called Kcnq2, which encodes a potassium channel -- that is, a tunnel that opens up in the cell membrane, enabling the passage of potassium ions. Potassium channels play a central role in the life of neurons, maintaining their stability and preventing their excessive firing.