Antidepressants need new nerve cells to be effective, UT Southwestern researcher

[Guest guest]

Antidepressants need new nerve cells to be effective, UT Southwestern

researchers find

http://www.eurekalert.org/pub_releases/2008-08/usmc-ann082708.php

Researchers at UT Southwestern Medical Center have discovered in mice

that the brain must create new nerve cells for either exercise or

antidepressants to reduce depression-like behavior.

In addition, the researchers found that antidepressants and exercise

use the same biochemical pathway to exert their effects.

These results might help explain some unknown mechanisms of

antidepressants and provide a new direction for developing drugs to

treat depression, said Dr. Parada, chairman of developmental

biology and senior author of a study in the Aug. 14 issue of the

journal Neuron.

In animals, it was already known that long-term treatment with

antidepressants causes new nerve cells to be generated in a part of

the brain called the dentate gyrus. Exercise, which can also relieve

the symptoms of depression, stimulates the generation of new nerve

cells in the same area.

" We would never claim that what we study in mice directly relates to

how antidepressants work in humans, but there are interesting

features in parallel, " Dr. Parada said. " The study unifies different

observations that point to the brain's dentate gyrus region and to

creation of nerve cells as being important in depression. "

Antidepressants act very quickly to increase levels of natural

compounds, called neurotransmitters, which nerve cells use to

communicate. It takes several weeks to several months, however, for

the patients who respond to such treatments to feel less depressed.

Dr. Parada said this implies that some other long-term mechanism is

also at work.

The current study was designed to test several phenomena that have

long been observed in animal studies but have not been studied

together to see if they are linked, Dr. Parada said.

The researchers focused on a molecule called TrkB, or Track-B, which

is found on the surface of nerve cells and responds to several growth

factors to cause new nerves to grow in the dentate gyrus.

They genetically engineered mice to lack TrkB specifically in the

stem cells that give rise to new neurons, then gave them

antidepressants for several weeks or allowed them to run on wheels.

When the mice were tested for depressive behavior, the tests revealed

that neither the antidepressants nor the exercise had helped them,

and the animals also had not grown new nerve cells in the dentate

gyrus.

" At least in mice, this result directly links antidepressants and

voluntary exercise with TrkB-mediated creation of nerve cells, " Dr.

Parada said.

The results also showed that antidepressants required TrkB to

stimulate the growth of new nerve cells.

Matching the timeframe for medicated patients to feel less depressed,

it takes several weeks for new nerve cells to grow, Dr. Parada said.

This parallel effect, he said, may mean that antidepressants need to

stimulate growth of new cells in the dentate gyrus in order to

achieve their full effect.

" We can get biochemical, physiological, behavioral and anatomical

results in animal models, " Dr. Parada said. " These all resonate with

the human condition, so perhaps you have a physiological relevancy.

" There could be a way to stimulate growth of nerve cells to fight

depression, for example. "