Stimulating brain circuits

Melatonin’s immediate precursor, N-acetylserotonin, can stimulate the same brain circuits activated by the growth factor BDNF and may provide another route for development of new antidepressants.

N-acetylserotonin (NAS) is produced by the neurotransmitter serotonin and is converted into melatonin with the help of several enzymes. NAS was thought to have no other function than acting as a precursor to the production of melatonin, but an Emory research team has shown that it stimulates the same circuits in the brain activated by BDNF (brain-derived neurotrophic factor). A lack of BDNF, which pushes brain cells to grow and helps them resist stress, is thought to lie behind depression and several neurodegenerative diseases.

The researchers, led by pathologist Keqiang Ye and pharmacologist Michael Iuvone, are looking for chemicals that mimic BDNF by activating TrkB, the receptor for BDNF on cells’ surfaces.

Several widely prescribed antidepressants (selective serotonin reuptake inhibitors such as fluoxetine/Prozac) increase levels of serotonin in the brain, but the connections between serotonin levels and depression are complex. Because antidepressants seem to take weeks to display their effects, scientists have proposed that their real targets are BDNF and TrkB.

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Emory Medicine Summer 2010