Study Uncovers More Clues About Antidepressants’ Action

There is little doubt that brain-derived neurotrophic factor (BDNF)—a neurotrophin that promotes neuronal maturation and synaptic plasticity—is also complicit in depression. Ample research has linked decreased levels of BDNF in the brain and blood with major depression (Psychiatric News, October 16, 2009).

Research also points to BDNF as a factor in the action of antidepressants. When mice were given antidepressants, they had increased BDNF levels in the dentate gyrus region of the hippocampus. The dentate gyrus is a tightly packed layer of small granulate cells that wrap around the end of the hippocampus.

And now scientists have found that antidepressants increased BDNF in another area of the hippocampus as well. It is the cornu ammonias (CA) 3 area.

The finding was reported February 8 in Neuropsychopharmacology. The study’s senior researcher was Enrico Tongiorgi, Ph.D., head of the Cellular and Molecular Neuroanatomy Lab at the University of Trieste in Italy.

Tongiorgi and his colleagues treated mice for two weeks with either the antidepressant fluoxetine or the antidepressant reboxetine and then assessed whether the treatments increased BDNF in the dendrites of CA3 neurons. They found that they did.

“Our results add one further piece of evidence to the neurotrophin hypothesis of antidepressant action in the hippocampus, which indicates the dentate gyrus–CA3 axis as a major biological substrate for an effective action of antidepressant treatments,” the scientists concluded. Their findings could also be used “to design more specific antidepressants” than those currently on the market, they suggested.

And since exercise is known to have an antidepressant effect, the scientists conducted an additional experiment in which they let mice exercise for 28 consecutive days. They examined the hippocampi of the mice and found that the exercise, like antidepressants, had increased BDNF in the dendrites of the CA3 neurons.

The research was funded by the Italian Ministry of University and Scientific Research.

An abstract of “Physical Exercise and Antidepressants Enhance BDNF Targeting in Hippocampal CA3 Dendrites: Further Evidence of a Spatial Code for BDNF Splice Variants” is posted at www.nature.com/npp/journal/vaop/ncurrent/abs/npp20125a.html.