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Week 1: Neurogenesis & Anti-depressant actions

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In 2003, Santarelli et al. confirmed the existence of a link between the stimulation of neurogenesis by antidepressants (ADs) and how this contributes to their behavioral effects. A mere five years later—though this may be considered eons in the fast-paced world of neurobiological and technological advancements—Bessa et al. published a rebuttal elucidating that ADs work even when neurogenesis was halted through administration of methylazoxymethanol (MAM). This critique pushed forth the theory that neuronal plasticity is more crucial than neurogenesis to experience behavioral effects of ADs. Nevertheless, it complimented the preceding idea with the stance that stimulation of adult hippocampal neurogenesis may be necessary, it is not sufficient to produce the behavioral effects of ADs.

To study the functional implication of such observations, Bessa et al. (2008) used an unpredictable chronic mild stress (CMS) paradigm to induce symptoms of depressive behaviors in rat models. Standard behavioral assays were used to assess anhedonia, learned helplessness, and anxiety-like behaviors. After the induction of stress, a recovery experiment commenced using four different antidepressants alongside the cytostatic drug MAM to attenuate neurogenesis. Characterization of therapeutic efficacy was done using mRNA expression studies of genes heavily implicated in synaptic remodeling and plasticity in the PFC (this is a step up from Santarelli et al. among other things).  

Although the mechanisms and pathology of depression still remain unclear, we know that both neural plasticity and neurogenesis are disrupted in depression. That being said, the findings of Bessa et al. are in accordance with those of Santarelli et al., though the difference in time period reflects the methodology and subsequent interpretation of the results acquired. From my understanding, Santarelli et al. completed what experimenters of the early 2000s would have deemed a proper and thorough investigation. The results are not inaccurate, but in due time we could see that they are also not complete. Bessa et al. took advantage of more modern-day techniques to assert that there’s more to the story than we initially thought. It’s only a matter of time before another scientist sees a hole in the combination of these two and sets forth an additional mechanism—being that depression is so complex.


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