Neurogenesis and antidepressant action - John Lambert


Santarelli et al.(2003) and Bessa et al. (2009) both present new research related to determining the mechanism of action for antidepressants (AD) in mice models. The mechanism for action is still not well understood, despite ADs being available for many decades and a multitude of hypotheses. These authors both examine one of the hypotheses; that neurogenesis within the hippocampus causes the behavioral effects of AD treatment. 
Santarelli et al. suggests that hippocampal neurogenesis, specifically in the SVZ and SGZ, is required for the behavioral effects of antidepressants to occur. Santarelli et al. lacks a Materials and Methods section, which makes it more difficult (if not impossible) to completely assess the validity of the research and the findings. I was extremely surprised by this, and I had difficulty comparing this paper to others partially because it was missing that entire section (though some information that would normally be there was found elsewhere in the paper). It was not clear how they induced depressive behavior in the mice for the first part of their experiment, and their later use of KO mice may have influenced some of their results. The use of irradiating the hippocampus to disrupt neurogenesis was extremely interesting to me; their results using this method lend support to the idea that neuronal propagation is necessary for AD behavioral effects. 
Bessa et al. refutes the findings of Santarelli, by using a variety of methods to indicate that the behavioral effects of ADs are not dependent on neurogenesis, but are at least partially caused by neuronal remodeling. Bessa et al. is a longer publication, the researchers conducted more experiments, the paper goes into more detail about the various experiments preformed, why they were preformed, and examines their findings more thoroughly as well. I liked the modified CMS paradigm that was used, as well as the methods and tests used to analyze changes in the mice over time. The use of MAM was well supported, but I agree with Dana, in that it may have caused some of the differences between these two papers. Bessa et al.  found that neurogenesis is not the only mechanism behind AD treatment. 
The massive differences in the findings of these two papers is likely due to the differences in protocols, methods, and approaches. I would have liked to have seen both papers include additional drugs that are used to treat depression, to see if they would alter any findings. Follow up studies are necessary to determine the actual mechanism behind the behavioral effects of ADs. 

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