Skip to main content

Week 1: Neurogenesis

By
Data suggests that neurogenesis continues into adulthood and is an essential process in which new neurons are derived, migrate, and inevitably integrate into circuits. It is interesting to note that although neurons and glia themselves are highly dynamic given their ability to rewire constantly, still new neurons are needed. This is especially relevant in the context of disease and disorder states, such as severe depression, in which brain atrophy is present. 
At first glance of  Santarelli et al. and Bessa et al., it is obvious that the functional relevance of neurogenesis is very hard to study. Both papers do show that neurogenesis occurs in the context of antidepressant treatment but struggle to establish a functional link between these new neurons formed and behavioral rescue of anhedonia and helplessness. This is in fact the exact rebuttal of Bessa et al. to Santarelli et al.’s claim that antidepressants work via neurogenic restoration. There is a major problem with this claim. The paper does make a good attempt at showing the necessity of neurogenesis in linking antidepressant’s improvement on NSF latency but, does not provide any functional relevance in the context of depression. For example, it would have been interesting to test the 5HT-1A receptor null mice using the CMS model in Bessa et al. or to prove that these serotonergic neurons are part of engrams responsible for overall anxiety, not just feeding behaviors. Down-regulating receptors and irradiating the hippocampus may cause brain-wide changes and labeling new mature neurons is not sufficient to prove that neurogenesis mediate antidepressants alone. 
Even though Bessa et al. contradicts the earlier link established between neurogenesis and antidepressant treatment, I think both parties would serve well to look into the role of these new neurons. In Bessa et al. it is partially concluded that these new neurons are indeed changing behavior but only robustly in NSF. But, without looking at the functional niche of these new neurons it is hard to claim that there is no link at all. As anxiety behaviors amongst individuals vary, so do their respective circuits. Possibly, these new neurons formed are associated with a specific anxiety pathway in which should be investigated further. Especially if neurogenesis is robust enough to change PFC volume, it is unfair to disregard it and claim that this is only neuronal/synaptic remodeling.
Overall, both papers do provide some convincing data in that neurogenesis is present but, it is intriguing to see how contradictory both papers really are. Many more experiments need to be done in order to truly establish a link with antidepressants, and truly understand the secondary mechanisms of action at play when these treatments are used. 

Comments

Post a Comment

Popular posts from this blog

Buffington et al (2016) and Reber et al. (2016)

By
This week's articles were about the role of the gut-brain axis in neurodevelopment and stress. Reber and colleagues used a heat-killed version of the bacteria, M. vaccae, as a type of vaccine and found that administration to mouse models resulted in decreased response to chronic stress, prevented colitis related to stress, and reduced measures of anxiety. Reber et al. also used the inactivated M. vaccae in a mouse model of IBD and found that the bacteria prevented stress-induce flare-ups of colitis, but that this could be reversed by removing T cells. Buffington and colleagues instead examined the role of gut microbiota in maternal high-fat diets (MHFD) in the neurodevelopment and social behaviors of their offspring. Buffington et al. found that housing MHFD rats with the offspring of regular diet (MRD) rats prevented social deficits in their offspring. They also found that this co-housing arrangement prevented an imbalance in the gut bacteria Reber and colleagues' findings w...
Post a Comment
Read more

Gut-brain axis

By
This weeks papers Reber et al. 2016 and Buffington et al. 2016 present a super interesting look into the gut-brain axis. Regarding both of these papers, it was amazing to see how potent favorable or unfavorable gut microbiome compositions are in affecting neuronal signaling and overall behavior. Reber et al. shows how immunoregulatory immunization with specifically heat killed M.vaccae can serve as a protective factor against chronic subordinate stress induce colotis as well as behavioral symptoms due to chronic stress as such. Interestringly, this paper depleted regulatory T cell activity via the anti CD25 antibody in order to show that the antiinflammatory mechanism induced by m vaccae immunization is depented on the secondary regulatory mechanisms offered by Treg proliferation and signaling. But, when T reg signaling was removed, this did not seem to cause a significant change in behavior . Therefore, this begs the consideration of what othe rmechanisms may be at play in order ...
Post a Comment
Read more

Gut-Brain Interactions: Buffington et al. (2016) and Reber et al. (2016)

By
Buffington et al. (2016) and Reber et al. (2016) present quite fascinating approaches to studying the interactions or ‘axis’ between the rodent (and human) gut and brain. As the gut is a primary route for bringing things from the environment into our body, these two studies present very clear and convincing evidence for the relevance and translatable validity of their various hypotheses.   One of the most interesting conclusions to me from Buffington et al. was that co-housing three high-fat diet offspring with just one regular-diet offspring was enough to rescue their social behavior deficits and microbiome profiles. This is remarkable, and I would like to hear more about possible mechanisms for this transfer to actually occur. Although the article mentions that mice do eat each other’s feces to transfer microbiota, could there be a certain “threshold” or level of bacteria needed to observe this phenotype switch? That is, how many more high-fat diet mice could have been house...
Post a Comment
Read more