Chronic social isolation reduces 5-HT neuronal activity via upregulated SK3 calcium-activated potassium channels

摘要

Major depressive disorder is a common and debilitating disease that interferes with the afflicted person’s everyday life. While some patients do benefit from antidepressant treatments, these medications need to be taken for several weeks before they become effective. Still, a large proportion of patients do not recover fully and some do not respond at all to the existing treatments. As a result, there is a need to find new and more effective treatments for depression. The most widely used antidepressant drugs target the chemical messenger or neurotransmitter called serotonin. The majority of nerve cells that produce serotonin are located in a region deep in the brain known as the dorsal raphe nucleus. When active, these nerve cells release serotonin; this in turn controls the cells’ own activity as well as the activity of a large number of connected nerve cells located throughout the brain. Any disruption in this system will have a widespread impact and can potentially increase the risk of disturbed moods. However, it was not exactly clear what alters the activity of serotonin-producing nerve cells in depression. Now, Sargin et al. have identified a previously unknown mechanism that underlies changes to the activity of serotonin-producing nerve cells. Keeping mice isolated for a prolonged period elicits the symptoms of depression. Sargin et al. found that serotonin-producing nerve cells were dramatically less active in isolated mice and that a specific type of ion channel protein (the SK3 channel) was more abundant in these nerve cells. A higher amount of this channel inhibits the activity of nerve cells. Blocking these inhibitory SK3 channels (using a drug that can be obtained from bee venom) restored normal activity in the serotonin-producing cells. Moreover, this treatment alleviated the depressive symptoms of the isolated mice. The findings of Sargin et al. suggest a new way to treat the symptoms of depression. Yet to translate them into an accessible treatment for patients, future work will be required to develop drugs that can specifically and potently target the affected channel.