Antidepressants need new nerve cells to be effective, UT Southwestern researchers find

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."

Other UT Southwestern researchers involved in the study were lead author Yun Li, graduate student in developmental biology; Bryan Luikart, former graduate student in developmental biology; Dr. Shari Birnbaum, assistant professor of psychiatry; Jian Chen, student research assistant in developmental biology; Dr. Chang-Hyuk Kwon, instructor of developmental biology; Dr. Steven Kernie, associate professor of pediatrics; and Dr. Rhonda Bassel-Duby, associate professor of molecular biology.

The work was supported by the National Institute of Neurological Disorders and Stroke.

Visit http://www.utsouthwestern.org/neurosciences to learn more about UT Southwestern's clinical services in neurosciences.

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Dr. Luis Parada -- http://www.utsouthwestern.edu/findfac/professional/0,2356,15510,00.html