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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 14 of 14. This is the beginning of the thread.
Posted by Phillipa on April 24, 2012, at 17:52:52
Yeast Cell Reaction to Zoloft Suggests Alternative Cause, Drug Target for Depression
Princeton University researchers have observed a self-degradation response to the antidepressant Zoloft in yeast cells that could help provide new answers to lingering questions among scientists about how antidepressants work, as well as support the idea that depression is not solely linked to the neurotransmitter serotonin.
In findings published in the journal PLoS ONE, researchers based in the lab of Ethan Perlstein, an associate research scholar in Princeton's Lewis-Sigler Institute for Integrative Genomics and senior lecturer in molecular biology, report that sertraline trademarked as Zoloft accumulated in the internal membranes of baker's yeast cells.
This buildup caused a swelling and sharp curvature in the membranes of vesicles, bubble-like cell components with a hand in cell metabolism, movement and energy storage. The vesicles then went into autophagy, a protective response in which cells recycle excess or damaged membrane.
But yeast cells lack serotonin, which is the primary target of antidepressants, Perlstein said. By observing a reaction to sertraline in an organism that does not contain the drug's conventional target, Perlstein and his co-authors have found significant evidence suggesting that antidepressants engage in pharmacological activity beyond regulating serotonin. Perlstein worked with co-first authors Jingqui Chen and Daniel Korostyshevsky, as well as Sean Lee, all three senior research specialists in Perlstein's lab.
Although antidepressants are known to regulate serotonin, it is not completely understood how antidepressants interact with the body's brain cells and what effect, if any, this activity has on treating depression, Perlstein said. Antidepressant accumulation has been observed in the membranes of human cells, the researchers report, but is considered benign.
If, however, the membrane curvature the researchers found has therapeutic significance in treating depression, then the cell membrane could present an additional target for next-generation antidepressants.
More immediately, Perlstein said, the activity of the drug in a serotonin-free organism supports existing research suggesting that depression might also be linked to diminished secretions of brain-derived neurotrophic factor (BDNF), a protein that regulates brain-cell growth.
Perlstein explains his findings as follows:
"The key finding of this paper is that the antidepressant sertraline/Zoloft accumulates within an organism lacking serotonin and induces autophagy, which is a protective mechanism cells use to recycle excess or damaged cell membrane. Specifically, we observed distortions, bulging and buckling in the membrane layer of vesicles inside cells treated with sertraline.
"We saw these effects in the yeast species Saccharomyces cerevisiae, or baker's yeast. Despite it being a simple, single-cell organism, the basic cellular 'plumbing' of yeast has been preserved by evolution in more complex organisms, including humans.
"In fact, the gene networks that we found modify vesicle formation in yeast cells in response to sertraline also exist in human cells, specifically neurons. Vesicle formation heavily influences the ability of neuronal synapses the tiny gapped connections between nerve cells to package neurotransmitters and prepare them for use in nerve-cell communication.
"Our finding that sertraline affects vesicle formation suggests a more expansive view of antidepressant function than is currently accepted.
"Dominant now is the monoamine hypothesis of antidepressant function, which was originally formulated in the 1960s and 1970s. It states that depression is the result of a chemical imbalance of neurotransmitters in the brain that may be corrected by artificially increasing the levels of serotonin, or other monoamine neurotransmitters, in the synapses. Sertraline belongs to a class of drugs called selective serotonin reuptake inhibitors (SSRI) that are thought to block the function of specific proteins that normally decrease serotonin levels in the synapses.
"However, the monoamine hypothesis fails to account for several key clinical observations of antidepressant activity, notably the lag time between the start of antidepressant treatment in patients and the onset of relief. Moreover, the monoamine hypothesis cannot explain the unexpected biological activity of antidepressants in simple organisms that lack serotonin such as baker's yeast.
"The work out of my lab captures a specific non-serotonin-based biological reaction to an SSRI. Granted, the synaptic serotonin transporter is one site where these drugs interact, but we show that's likely not all they do. These drugs have multiple effects on various targets in the cell and one of the targets might be cell membranes themselves.
"In addition, our work provides some grounding for t he neurotrophic hypothesis of depression, which states that the loss of neural connectivity in specific brain regions such as the hippocampus may actually be the root of depression. The neurotrophic hypothesis fills in many of the gaps of the monoamine hypothesis, including the therapeutic time lag. Since the 1990s, neuroscientists have known that chronic, extended antidepressant treatment can result in the proliferation of brain cells, possibly via a mechanism that involves the growth protein BDNF.
"Altogether, our work suggests that the serotonin-based theory might be an oversimplification and that the cause of depression is not a closed story.
"In my lab, future research will aim to integrate the multiple, interwoven strands that make up the totality of antidepressant pharmacology including but also beyond serotonin and translate this knowledge into better antidepressants and diagnostic tools for depression."
Source: Princeton University
Posted by ron1953 on April 24, 2012, at 18:05:19
In reply to Zoloft or Ad's New Theory? Don't Understand?, posted by Phillipa on April 24, 2012, at 17:52:52
This is so typical in "science", where theories are constantly replaced by new theories - "oops, sorry, we were wrong". It's a fricken joke.
Posted by ron1953 on April 24, 2012, at 18:24:21
In reply to Re: Zoloft or Ad's New Theory? Don't Understand?, posted by ron1953 on April 24, 2012, at 18:05:19
Fact is that for over SIXTY years, virtually no progress has been made to produce effective antidepressants, and the new ones are no better than the older ones, besides perhaps having fewer and less severe side-effects. But the Big Pharma spin makes it look a lot different than it really is - people (including doctors and therapists) buy into the hype, with the results being a true fiasco.
Sure, like a lot of people, I wish these pills worked, but I cannot ignore the historical record, nor the outright lies.
Posted by zazenducke on April 24, 2012, at 19:09:02
In reply to Zoloft or Ad's New Theory? Don't Understand?, posted by Phillipa on April 24, 2012, at 17:52:52
Princeton University researchers have observed a self-degradation response to the antidepressant Zoloft in yeast cells that could help provide new answers to lingering questions among scientists about how antidepressants work, as well as support the idea that depression is not solely linked to the neurotransmitter serotonin.
....but antidepressants don't work for the vast majority of people! The research is interesting but the author's conclusions are ridiculous. This mechanism is just as likely to be causing chronic brain injury and other side effects.
Big Pharma probably has the ad department drawing up adorable lil vesicles with happy faces to sell more Zoloft with another unproved theory.Anyone know who financed this research?
Posted by linkadge on April 24, 2012, at 19:33:09
In reply to Re: Zoloft or Ad's New Theory? Don't Understand?, posted by zazenducke on April 24, 2012, at 19:09:02
The problem is that the article doesn't actually propose a theory. They simply state the observation that cells exposed to zoloft start to act abnormally.
And the above poster is right. They are (incorrectly) starting with the assumption that the drugs actually work.
Linkadge
Posted by sigismund on April 24, 2012, at 20:02:20
In reply to Re: Zoloft or Ad's New Theory? Don't Understand?, posted by ron1953 on April 24, 2012, at 18:24:21
>Fact is that for over SIXTY years, virtually no progress has been made to produce effective antidepressants, and the new ones are no better than the older ones,
Anything likely to be effective or any good would immediately become a drug of abuse. For a while yet.
Posted by Phillipa on April 24, 2012, at 21:26:50
In reply to Re: Zoloft or Ad's New Theory? Don't Understand?, posted by sigismund on April 24, 2012, at 20:02:20
I borrowed the article from another site. Sigi you get it too? PJ
Posted by gadchik on April 25, 2012, at 8:01:08
In reply to Re: Zoloft or Ad's New Theory? Don't Understand?, posted by Phillipa on April 24, 2012, at 21:26:50
I really feel that we are on our own and I wish a bright new mind would get into research and figure out what will work!
Posted by linkadge on April 25, 2012, at 16:29:20
In reply to Re: Zoloft or Ad's New Theory? Don't Understand?, posted by gadchik on April 25, 2012, at 8:01:08
The problem is that it is a buisness. If drug developement were based on compasionate grounds, we would develop synthetic hyperforin (st. john's wort) and it would be the next blockbuster.
Linkadge
Posted by papillon2 on April 25, 2012, at 18:16:28
In reply to Zoloft or Ad's New Theory? Don't Understand?, posted by Phillipa on April 24, 2012, at 17:52:52
> Yeast Cell Reaction to Zoloft Suggests Alternative Cause, Drug Target for Depression
>
> Princeton University researchers have observed a self-degradation response to the antidepressant Zoloft in yeast cells that could... support the idea that depression is not solely linked to the neurotransmitter serotonin.No sh*t Sherlock! I mean, seriously? Any person worth their Lithium salt (sorry, had to make the joke) knows that there is more to it than seretonin. Even those solely wedded to the (overly simplistic!!!) idea of neurotransmitter disfunction still add norepinephrine and dopamine to the mix.
Wow, just wow.
Posted by linkadge on April 25, 2012, at 20:02:55
In reply to Re: Zoloft or Ad's New Theory? Don't Understand?, posted by papillon2 on April 25, 2012, at 18:16:28
Well, I guess we need the Princeton name on it before its official :)
Linkadge
Posted by Phillipa on April 25, 2012, at 20:47:03
In reply to Re: Zoloft or Ad's New Theory? Don't Understand?, posted by linkadge on April 25, 2012, at 20:02:55
As I said I literally stole it from another site like babble. Since no names or addressed involved I wanted to see what you thought. Thanks Phillipa
Posted by linkadge on April 26, 2012, at 19:39:22
In reply to Re: Zoloft or Ad's New Theory? Don't Understand? » linkadge, posted by Phillipa on April 25, 2012, at 20:47:03
because right now psychiary does= ssris.
Linkadge
Posted by bleauberry on April 27, 2012, at 18:08:24
In reply to Zoloft or Ad's New Theory? Don't Understand?, posted by Phillipa on April 24, 2012, at 17:52:52
I think for every thing we know about meds, depression, brain, etc, all of it is maybe not even 10% of what's really there that we don't yet know.
For example, with Zoloft, what we think we know about it is dwarfed by what we don't know.
Observations such as in this article and others I think give us hints of the vastness of stuff we don't know. But we're learning new stuff every day, both in the lab and in our own battles.
This is the end of the thread.
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