Week 1: Santarelli and Bessa

In reading both of these papers I came to similar conclusions that Ella and Matt G. stated in their responses. Yes, it does seem as though in comparison to Bessa's paper Santarelli's lacked completeness and scientific depth. And yes, I agree that it seems there is much more to the story of anti-depressants than just neurogenesis. However, unlike both Ella and Matt G., I do not think the Santarelli paper is shortsighted or lacking in validity. 

The Santarelli paper does a great job at identifying how neurogenesis and anti-depressants work together in the hippocampus. I particularly appreciated the discussion of their results in light of two experimental “dissociations” – one being that “5-HT1A KO mice show higher levels of anxiety-related behaviors in the NSF test but have WT levels of basal neurogenesis”; and the other that “a 28-day ablation of neurogenesis in vehicle-treated mice does not produce any behavioral deficit in either the NSF or CUS test”. I thought their theory as to why the 5-HT1A KO mice would show no change in behavior even with WT levels of neurogenesis was spot on and made a lot of sense – after all, if the KO mice lacked this receptor from birth, it would make sense that it has some influence on how the area developed and as such new neurogenesis in that region may not have the same effect as neurogenesis in a WT mouse. This is entirely plausible even if the neurogenesis is at the same level. Additionally, their explanation as to why irradiation of vehicle-treated mice does not result in depressive like tendencies made a lot of sense to me as well. It seems as though Santarelli was suggesting that yes neurogenesis is essential for the effectiveness of AD’s, it may have to do with a NEW type of neurogenesis in response to AD’s that may have been different than the type of neurogenesis present in WT/baseline conditions. With this caveat put forth in the Santarelli paper, I think the Santarelli paper and the Bessa paper have more in common than at first it may seem.

Some responses to the papers seem to put the two at odds with each other, because the Bessa paper seems to be advocating that neurogenesis is not necessary and the Santarelli paper is remarking the opposite. Assuredly, the Bessa results as to the elimination of CMS-induced behavioral signs of depression to an equal extent in vehicle and MAM-treated mice is indicative that not all anti-depressant effects are modulated by neurogenesis. However, their next conclusion that neurogenesis is necessary for the reduction of anxiety-like behavior in CMS-exposed rats lines up closely with Santarelli’s work, and is indicative that some of effects of ADs are dependent on neurogenesis. It could be in comparing the two it is better not to say they are at odds with each other (because I do not think that is the case in their findings at all) but rather Santarelli isolated data showing that neurogenesis plays an essential part in AD effects, and Bessa indicated that the specific AD effects neurogenesis is necessary for is in its alleviation of anxiety symptoms. Bessa’s paper said itself that anxiety is often present with depression, and it could be that AD’s effects on neurogenesis work to negate this common problem in depression-like disorders.