Beer Yeast and Zoloft

Beer Sampler (I took this picture)

Yeast is an amazing organism that converts sugar into ethanol, or in other words barley into beer. It is used to ferment beer and is then usually filtered out.  (The leftmost beer sample in the picture above is an unfiltered beer and is cloudy because of the yeast still floating in it). 

Aside from providing proof that god loves us and wants us to be happy, yeast also provides a fascinating model in which scientists can study specific cellular processes. Because it is a simple eukaryote and can be easily cultured and easily mutated, yeast has long been used to test the effects of genetic manipulation on eukaryotic intracellular workings.

(source)

However, it's not often thought that yeast would be a good model for studying processes specific to the brain. But a recent paper published in PLoS One uses yeast to test the cellular actions of anti-depressants.  Specifically, they apply Zoloft to yeast cells.

Zoloft (like Prozac and other highly prescribed anti-depressants) works as a selective serotonin reuptake inhibitor (SSRI), inhibiting the uptake of serotonin after it has been released into the synapse, functionally allowing more serotonin to remain in the synaptic cleft. 

But Yeast don't have serotonin receptors and they don't have synapses. So what on earth could Zoloft do in these cells?

("Zoloft Does Everything" from Hipstercards.com)

Well here's a possibility: maybe Zoloft doesn't just alleviate depression by inhibiting the re-uptake of serotonin.  Maybe it does something else too. And if you are looking for non-serotonergic actions of Zoloft, yeast becomes the perfect organism to experiment on.

One reason to think there might be other (non-serotonergic) effects is that Zoloft takes a while to start 'working'.  That is, when Zoloft is taken, the enhancement of serotonin is almost immediate, but the actual effect on depressive symptoms can take weeks to appear.

So the question is: Are there effects of Zoloft which take a while to appear and do not specifically involve serotonin? 


Well, yes, there are.  Zoloft actually accumulates in the membrane of yeast cells, often killing them.  Which... doesn't sound promising. But Chen et al., 2012 shows that this membrane accumulation doesn't always kill the yeast cell and that in some select situations the membrane accumulation could have a protective effect by triggering cell-repair activities.  At "sub-lethal" doses, Zoloft can partially rescue stunted growth in certain yeast mutants.


This work seems to support the neurotrophic hypothesis of depression which says that neurons die depression, and that anti-depressants actually "reduce neuronal atrophy"
Does this paper show that Zoloft prevents neuronal death? No, not at all. It is investigating yeast, and shows that Zoloft could in some situations trigger cell repair.  But it doesn't say that Zoloft acts this way in neurons.


Obviously a lot more work needs to be done to really understand the actions of Zoloft and other anti-depressants. This study in yeast is a first step, but the findings need to be extended actual neurons before the trophic mechanism of Zoloft becomes anywhere close to as convincing as the SSRI mechanism. 

© TheCellularScale

Chen J, Korostyshevsky D, Lee S, & Perlstein EO (2012). Accumulation of an antidepressant in vesiculogenic membranes of yeast cells triggers autophagy. PloS one, 7 (4) PMID: 22529904