Nerve cells need to be under control
It has long been known that depression is caused by an imbalance in the brain’s neurotransmitter system, the function of which is to optimise the communication between the brain’s nerve cells, known as neurons.
Some neurotransmitters activate the neurons while others inhibit them. This can be compared to the accelerator and brake pedals in a car. These pedals balance the neuronal activity.
If the brain is healthy, it can push either of these pedals down as needed. But if it’s in a depressive state, at least one of the pedals is defective. And in order to get better, the faulty pedal needs to be repaired.
It’s known that the hippocampus region in the brain plays a key role in the development of a depression. By removing the animals’ brains and manipulating specific neurons in them, the researchers at Aarhus University in Denmark discovered a defective neurotransmitter, GABA, which is known to contribute to the control of the communication between two types of nerve cells, interneurons and granule cells.
“The hyperactive cells release the substance glutamate, which kill neurons. When a part of the brain cells in the area die, the hippocampus starts to shrink. And since the hippocampus is heavily involved in the generation of our emotions and memory, we develop a depression. We become sad and we have difficulties remembering things.”
It’s all about communication
The discovery was made during examinations of thin hippocampal brain slices from laboratory rats. Since the brain slices were still alive, the researchers were able to stimulate the nerve cells in various ways to determine whether they were functioning as they should or whether they were defective.
The stimuli consisted of small electrical shocks, strong enough to put the nerve cells’ brake pedal back into motion.
As expected, the healthy nerve cells responded to the shock by releasing sufficient amounts of GABA. The cells in the depressed animals, on the other hand, did not respond. Their braking effect was clearly reduced.
”According to our measurements, granule cells are more active in the depressed animals than they should be,” says Wiborg.
“This means that in the sick animals, the cells communicate more with other regions of the brain than they should. And it’s this hyperactivity that provokes cell death, which then leads to depression.”
Antidepressants repair the brake
When the researchers gave antidepressants to the depressed rats, the GABA brake regained its power over the granule cells. The brain regions started communicating normally again and then the depression disappeared.
Great expectations for the braking system
The SSRI drugs such as Citalopram or Prozac that were originally targeted at the serotonin system appear in some cases to also be capable of repairing a defective GABA brake, but that’s not good enough because it only helps some patients.
For many years, sleeping pills have been prescribed to patients with anxiety, but the problem here is that it makes them drowsy. If, instead, we could target the brain’s built-in brakes, the patient might recover without the strong side effect.
”Our goal is to develop new drugs that can function as an alternative to antidepressants, and which can be targeted to those patients who do not respond to SSRI. We are currently running some very exciting studies on that front,” says Jensen.
(Source news:sciencenordic.com)
(Source picture:unsplash.com)
