Week 1 Lucia Ryll

I started with the Bessa paper, and after working through the weirdly worded second sentence, I found myself enjoying the experiments. What I liked about this paper was that the authors clearly stated their goal, and proposed one simple way to test their hypothesis: using MAM at a dose of 7 mg/kg per day to reduce neurogenesis and so prove that antidepressants can function without neurogenesis. However, this led me to some questions. First, the MAM treatment at this dose was said to reduce neurogenesis by 60% in the dentate gyrus. Although I am not familiar with the amounts of neurogenesis needed, I feel that the authors should have elaborated on why they believe this 60% reduction (in only the dentate gyrus?) is enough for them to claim that hippocampal neurogenesis is no longer playing a role in the mechanism of the antidepressants. In their discussion, the authors mention that the antidepressants actually stimulated neurogenesis beyond the levels of controls. They then claim that this may be coincidental or mediated through other mechanisms because concomitant MAM treatment did not prevent the therapeutic effects of the antidepressants. Although I think this sounds good, and I think the data throughout the paper seems solid, I hesitate to think that a 60% reduction in neurogenesis is enough to say that it has no contribution.

-- After reading the Santarelli paper, I now understand that the dentate gyrus is the primary area of the hippocampus that allows neurogenesis. So, it makes more sense that 60% reduction would have a significant enough impact on neurogenesis.

Ok, now I have finished Santarelli and I have to say, I find it more difficult to compare these two papers than I anticipated. First off, the Santarelli experiments use wild-type mice treated with antidepressants to show that the AD treatments increase neurogenesis. I would suspect that treating WT mice with AD might have a different effect than treating depressed mice with AD as was done in the Bessa paper. Santarelli et al also use a different method of blocking neurogenesis, namely x-irradiation of the hippocampus, which caused an 85% reduction in progenitor cells in the SGZ. I would be curious to see an experiment set up like in Bessa et al (testing anhedonia, learned helplessness, and anxiety) with a comparison of MAM treated and x-irradiation effects on antidepressant treatments. Maybe this could clear up the question of whether it is a difference of strength of the remaining neurogenesis, or any disruption to neurogenesis itself, that affects the mechanism or efficacy of antidepressant treatments. Lastly, I was disappointed that the Santarelli paper only used the NSF test for depression, the way this was approached in the Bessa paper seemed more logical and convincing to me, although I wouldn’t say that I’ve been fully convinced of either paper.