Nav: Home

New antidepressant target discovered

July 12, 2016

  • Decreasing set of proteins reduces depression in mice
  • Gene therapy turns off channels in hippocampus to improve mood
  • Scientists working on adapting gene therapy for clinical use
CHICAGO --- Northwestern Medicine scientists have shown how manipulating a novel target in the brain using gene therapy could lead to new treatments for depression.

The investigators showed decreasing a set of proteins called HCN channels reduced depression-like behavior in mice. If replicated in humans, the findings could inform fresh therapies for millions of patients who do not respond to existing treatments for depression.

"Drugs currently available for treating depression help most patients, but they stop working for some patients and don't work from the get-go for others," said senior author Dr. Dane Chetkovich, ?a professor of neurology and of physiology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine neurologist. "There is a real need for new therapies to help patients desperate for alternatives to the available therapeutic options."

The study will be published July 12 in the journal Molecular Psychiatry.

Most existing antidepressants affect mood and emotions by increasing levels of neurotransmitters called monoamines, namely serotonin, dopamine and norepinephrine. But the fact that these drugs are not effective for many patients suggests there are additional mechanisms underlying depression yet to be uncovered that could be targeted with new therapies.

In previous research, Chetkovich's lab and others showed those mechanisms might involve the hippocampus, a region of the brain important for learning, memory and emotional regulation. There, they saw changes to HCN channels, typically involved in controlling the electrical activity of cells in the heart and brain, also played a critical role in behaviors linked to depression.

In the new study, a group of Northwestern scientists led by Chetkovich took steps to translate that insight into a potential gene therapy using mouse models. The scientists surgically injected mice with a nontoxic virus engineered to express a gene that turns off HCN channel function in hippocampus neurons.

"When the HCN channels stopped working, the mice behaved as if they'd been given antidepressant medications," Chetkovich explained.

In contrast, increasing the function of HCN channels removed the antidepressant effect.

To measure depression-like behavior, the scientists measured how long mice would seek to escape an environment before giving up -- a test commonly used by the pharmaceutical industry to screen compounds for effectiveness as antidepressants, including medications currently on the market.

"This work not only identifies a totally new treatment target for depression, it provides a detailed molecular description of the structures that need to be manipulated for it to act as an antidepressant and develops viral tools to do so," said Chetkovich, who is also director of Feinberg's Medical Scientist Training Program.

In future research, the scientists are focusing on adapting the viral gene therapy approach to human patients. They also have a grant from the National Institute of Mental Health to find small molecules that could be developed into oral medications to turn off HCN channels in the brain.
-end-
Other Northwestern authors of the study include Ye Han, Robert Heuermann, Kyle Lyman, Daniel Fisher and Quratul-Ain Ismail.

This research was supported by National Institutes of Health grants 2R01NS059934, R01MH106511, R21MH104471 and 2T32MH067564, Brain Research Foundation grant SG 2012-01 and Chicago Biomedical Consortium grant HTS-004.

NORTHWESTERN NEWS: http://www.northwestern.edu/newscenter/

Northwestern University

Related Depression Articles:

A biological mechanism for depression
Researchers report that in depressed individuals there are increased amounts of an unmodified structural protein, called tubulin, in lipid rafts compared with non-depressed individuals.
Depression in adults who are overweight or obese
In an analysis of primary care records of 519,513 UK adults who were overweight or obese between 2000-2016 and followed up until 2019, the incidence of new cases of depression was 92 per 10,000 people per year.
Why stress doesn't always cause depression
Rats susceptible to anhedonia, a core symptom of depression, possess more serotonin neurons after being exposed to chronic stress, but the effect can be reversed through amygdala activation, according to new research in JNeurosci.
Which comes first: Smartphone dependency or depression?
New research suggests a person's reliance on his or her smartphone predicts greater loneliness and depressive symptoms, as opposed to the other way around.
Depression breakthrough
Major depressive disorder -- referred to colloquially as the 'black dog' -- has been identified as a genetic cause for 20 distinct diseases, providing vital information to help detect and manage high rates of physical illnesses in people diagnosed with depression.
CPAP provides relief from depression
Researchers have found that continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea (OSA) can improve depression symptoms in patients suffering from cardiovascular diseases.
Post-natal depression in dads linked to depression in their teenage daughters
Fathers as well as mothers can experience post-natal depression -- and it is linked to emotional problems for their teenage daughters, new research has found.
Being overweight likely to cause depression, even without health complications
A largescale genomic analysis has found the strongest evidence yet that being overweight causes depression, even in the absence of other health problems.
Don't let depression keep you from exercising
Exercise may be just as crucial to a depression patient's good health as finding an effective antidepressant.
Having an abortion does not lead to depression
Having an abortion does not increase a woman's risk for depression, according to a new University of Maryland School of Public Health-led study of nearly 400,000 women.
More Depression News and Depression Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.