Antidepressants and Hippocampal Neurogenesis

   Neurogenesis pioneer, Luca Santarelli, MD, PhD, and his team, made an outstanding job showing that antidepressants (ADs), such as fluoxetine, can increase neurogenesis in the dentate gyrus hippocampus of mice.  He did so by incorporating 5-bromo-2’-deoxyuridine (BrdU) from increased number of progenitor cells, which would then differentiate into neurons and then become incorporated into neuronal circuits. Interestingly, fluoxetine did cause a 60% increase in amount of BrdU-positive cells in the dentate gyrus of the mice’s hippocampus, but only when these mice were treated for 11 or 28 days. This makes sense since in a clinical setting, it was shown that Ads could take an estimation of 3 weeks to have fully efficacy. In depression subjects, selective serotonin reuptake inhibitor (SSSI), such as fluoxetine, can change neuronal gene expression when it comes to long term of SSSI, which can explain the reason why fluoxetine takes a while in order increase neurogenesis in the hippocampus.

   When Santarelli and his team decided to test whether the effects of serotonin and norepinephrine enhancing ADs in mice that would be lacking 5-HT_1A receptor, which is one of the subtypes of 5-HT receptor, the results were not that far of the ordinary. The results showed that 5-HT_1A receptor knockout (KO) mice that were given fluoxetine did not cause an increase in BrdU-labeled cells, but there was an increase in BrdU-labeled cell in mice with a functioning 5-HT_1A receptor. Even though when these two genotypes of mice were given imipramine there was an increase BrdU cells. I believe the reason for that is because imipramine is a strong noreprephrine reuptake inhibitor and adrenergic receptors, which targets noreprephrine. But since fluoxetine is a SSSI, mice lacking 5-HT_1A receptor would not be able benefit from a SSSI antidepressant. It would be interesting if he and his team.

   Over all, I enjoyed reading this article and it helped me apply the knowledge I have about depression by thinking critically to the results they acquired and think about the techniques that are used to identify the formation of new neurons.