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Brain stimulation successfully treats depression in mice

  • Scientists at the Children’s Hospital of Philadelphia found that a pathway linked to memory is also linked to mood
  • By stimulating proteins in that pathway they triggered ‘antidepressive behavior’ in mice
  • The researchers say this could pave the way to drug-free alternatives

Scientists have successfully treated depression in mice using brain stimulation – paving the way to a drug-free alternative for mental health care. 

Tens of millions of Americans are hooked on highly-addictive and costly medication that relieves their anxiety and depression but triggers debilitating withdrawal symptoms if they try to come off. 

As the rate of depression soars in America, scientists are scrambling to identify alternative treatments for patients. 

Now, a team at the Children’s Hospital of Philadelphia (CHOP) has shown that a pathway in brain circuitry can be stimulated to create ‘antidepressive’ behavior in animals.

A team at the Children’s Hospital of Philadelphia has shown a brain pathway can be stimulated to create ‘antidepressive’ behavior in mice, sparking hope for drug-free treatment in humans

The study, published today in Nature Medicine, has been hailed as a potential breakthrough in mental health care.

‘Major depressive disorder is a serious health problem worldwide. Existing treatments are helpful for many people, but also have a high rate of relapse and significant side effects,’ said study leader Dr Amelia J Eisch, a neurobiology researcher at Children’s Hospital of Philadelphia (CHOP).

‘Because scientists consider depression to be caused by malfunctions in brain circuitry, we suggest that “tuning” a specific circuit could set the stage for a targeted treatment.’  

Dr Eisch’s team focused on a circuit connected to the hippocampus, which controls mood and memory.

Since targeting the human hippocampus directly has proved disastrous in previous studies, Dr Eisch’s team decided instead to target a ‘region upstream’ from the hippocampus in lab mice. 

Stimulating this pathway (called Ent) is already known to improve memory and learning, but this is the first study to see how it affects mood.

They started by looking at mice in stress, and found that there is a protein in this pathway that increases during stress, and blocks signals.

To test this connection, the team put lab mice through a series of grueling experiments. Half these mice had been genetically-engineered to produce none of this blocking protein, and the other half were controls.  

There was a forced swim test, in which a researcher watched how a mouse behaved after being placed in a beaker of water. Each mouse kept moving until it became immobile and floated. Those who were deemed ‘antidepressive’ kept swimming for longer before giving in. 

In a feeding test, a mouse that is less anxious approaches a food pellet faster than an anxious mouse; the researchers regard mice that more readily approach something pleasurable as showing more antidepressive behavior.

‘Our findings are the first evidence that targeting this particular brain circuit may offer a potential new depression treatment,’ said first author Sanghee Yun, PhD.

‘This is a first step, so there is much research to be done to determine if we can translate this knowledge into practical, noninvasive treatments for people with depression,’ Dr Eisch said.

She added: ‘Existing brain stimulation therapies for depression are extremely helpful for many patients, but they don’t work for everyone, and they also have side effects such as memory loss and cognitive impairment. 

‘It is important to increase the number of tools available to treat depression, and find those with fewer side effects as well.’