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Neurogenesis & Anti-depressant Actions

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            The two papers presented this week were essentially discussing whether or not neurogenesis was the mechanism for the ameliorating effects of antidepressants (ADs). Before delving into their experiments, I want to note the timeline - the Santarelli paper was published in 2003 and the Bessa paper was published in 2009. The reason I find the timing so interesting is because the papers had similar results, but the second paper was able to build upon the first, and thus had more tests and was able to come to a different conclusion. It is the progression of scientific research and questioning current research that leads to new discoveries.
            To briefly summarize, Santarelli and collaborators used the novelty-suppressed feeding (NSF) test to analyze the effects of antidepressants on mice. After establishing the effects of the ADs, the researchers used irradiation of the hippocampus (specifically the SGZ) to show that there was a reduction in cell proliferation. In the irradiated mice, the ADs had no effect on the NSF test. From their experiments, Santorelli concluded that neurogenesis must therefore play a role in the effect of antidepressants. Six years later, Bessa and collaborators used the NSF test, anhedonia, and the forced swimming test (FST) to analyze the effects of ADs. This paper also states the importance of neurogenesis and its role in the effects of ADs, but instead of concluding that neurogenesis must be the mechanism for the effects, Bessa and collaborators explained that neurogenesis in the hippocampus may integrate into neuronal networks implicated in emotional behavior and therefore modulate anxiety. This, however, is not the mechanism of ADs. Rather, after more experiments, Bessa concludes that synaptic remodeling and plasticity might be the mechanism of ADs. 
            Both papers logically make sense, and I was curious as to if this “debate” was settled post-2009. I found a paper published in 2018 by Micheli and collaborators titled “Depression and adult neurogenesis: Positive effects of the antidepressant fluoxetine and of physical exercise.” I’m not concerned by the actual experiment in that paper itself, but with the background section. I was surprised to see all the experiments reporting the correlation between antidepressants and neurogenesis, and the role neurogenesis plays in anxiety and depression. The paper also mentions, though, that there is evidence that not all antidepressant actions require neurogenesis, and that depleting neurogenesis does not cause depression-like symptoms. In fact, the paper states that some antidepressants, such as fluoxetine, which was studied in both papers above, have a dual effect of being able to enhance the generation of new neurons in addition to facilitating synaptic plasticity. So, it seems like both papers, although with seemingly opposite views, actually complement each other and contribute to the knowledge we have about ADs and neurogenesis.

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