Boosting Depression-Causing Mechanisms in the Brain Increases Resilience, Surprisingly

Posted on April 23, 2014

A new study points to a conceptually novel therapeutic strategy for treating depression. Instead of dampening neuron firing found with stress-induced depression, researchers demonstrated for the first time that further activating these neurons opens a new avenue to mimic and promote natural resilience. The findings were so surprising that the research team thinks it may lead to novel targets for naturally acting antidepressants.

Researchers from the Icahn School of Medicine at Mount Sinai point out that in mice resilient to social defeat stress (a source of constant stress brought about by losing a dispute or from a hostile interaction), their cation channel currents, which pass positive ions in dopamine neurons, are paradoxically elevated to a much greater extent than those of depressed mice and control mice.

This led researchers to experimentally increase the current of cation channels with drugs in susceptible mice, those prone to depression, to see whether it would enhance coping and resilience. They found that such boosting of cation channels in dopamine neurons caused the mice to tolerate the increased stress without succumbing to depression-related symptoms, and unexpectedly the hyperactivity of the dopamine neurons was normalized.

The research team used optogenetics, a combination of laser optics and gene virus transfer, to control firing activity of the dopamine neurons. When light activation or the drug lamotrigine is given to these neurons, it drives the current and neuron firing higher. But at a certain point, it triggers compensatory mechanisms, normalizes neuron firing, and achieves a kind of homeostatic (or balanced) resilience.

"To our surprise, we found that resilient mice, instead of avoiding deleterious changes in the brain, experience further deleterious changes in response to stress, and use them beneficially," said Ming-Hu Han, PhD, at Icahn School of Medicine at Mount Sinai, who leads the study team as senior author.


Category(s):Depression

Source material from Mount Sinai Medical Center


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