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Secret of Prozac's Success Revealed (increases neural stem cell progeny)
Scientific American ^ | May 16, 2006 | NA

Posted on 05/17/2006 10:24:44 PM PDT by neverdem

New research in specially bred mice has elucidated how the antidepressant Prozac works. Scientists have long known that in addition to discouraging synapses from reabsorbing the neurotransmitter serotonin, Prozac (known generically as fluoxetine) also increases the number of neurons (neurogenesis) in the adult brain. But exactly how the drug manages this multiplication trick has proved difficult to pin down. Now researchers have traced the development cascade of new neurons and determined where fluoxetine exerts its multiplying--and beneficial--effect.

Grigori Enikolopov at the Cold Spring Harbor Laboratory and his colleagues bred a new strain of mice that allowed them to track the development of mature neurons from stem cells using the different marker proteins expressed. Of the six stages of neuron development observed in this process, the scientists found that more than two weeks of fluoxetine treatment boosted the number of so-called amplifying neural progenitors (ANPs) by nearly 50 percent (a migratory stream of which is shown in the image above).

Subsequent testing in mice allowed to live for a month after fluoxetine treatment showed a similar increase in the overall number of neurons. "Together, these results suggest that the fluoxetine-induced increase in the number of ANP precursors in the [brain] later translates into an increase in the number of new neurons," the researchers write in the paper presenting the findings in the Proceedings of the National Academy of Sciences.

By isolating the step in neuron development that fluoxetine influences, the scientists have identified a new target for antidepressants that may have fewer side effects. The research also unveils the links in the chain leading from stem cells to new neurons as well as provides an animal tailor-made to investigate the mechanisms of other medicines and treatments, permitting a ray of hope into the darker regions of brain dysfunction.


TOPICS:
KEYWORDS: medicine; neuralstemcells; science
Fluoxetine targets early progenitor cells in the adult brain PNAS pdf
1 posted on 05/17/2006 10:24:48 PM PDT by neverdem
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To: neverdem

del shannon knows...


2 posted on 05/17/2006 10:27:22 PM PDT by kinoxi
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To: neverdem

Those must be some really happy mice on drugs (what, with all the experiments and the lab they are stuck in)


3 posted on 05/17/2006 10:30:26 PM PDT by Panerai
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To: neverdem

Interesting. Thanks!


4 posted on 05/17/2006 10:31:43 PM PDT by patriciaruth (http://www.freerepublic.com/focus/f-news/1562436/posts)
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To: neverdem

I don't know, but my sister-in-law is weird, whether she's on Prozac or off...


5 posted on 05/17/2006 10:33:21 PM PDT by sageb1 (This is the Final Crusade. There are only 2 sides. Pick one.)
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To: neverdem
"Subsequent testing in mice allowed to live for a month after fluoxetine treatment showed a similar increase in the overall number of neurons." Yeah, can't let those little buggers live long enough to take over the experiment ... shades of Algernon's Revenge!
6 posted on 05/17/2006 10:34:10 PM PDT by MHGinTN (If you can read this, you've had life support from someone. Promote life support for others.)
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To: neverdem

Hope at last, my two surviving neurons might settle down and breed . . .


7 posted on 05/17/2006 10:42:10 PM PDT by dighton
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To: El Gato; Ernest_at_the_Beach; Robert A. Cook, PE; lepton; LadyDoc; jb6; tiamat; PGalt; Dianna; ...
Jill Stanek: The biggest boobs You need to check the pic in comment# 21.

Death's Waiting List

Microbes Convert Wastewater into Useable Electricity For anyone that's interested, I linked what I believe is the original, actual article on that thread.

FReepmail me if you want on or off my health and science ping list.

8 posted on 05/17/2006 10:50:46 PM PDT by neverdem (May you be in heaven a half hour before the devil knows that you're dead.)
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Comment #9 Removed by Moderator

To: grey_whiskers

*Pant pant* Image....too....big....


10 posted on 05/17/2006 11:22:26 PM PDT by DaveLoneRanger ("You're not going crazy! You're going sane in a crazy world!" - The Tick)
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To: Coleus

Pingo. G'night-o.


11 posted on 05/17/2006 11:23:52 PM PDT by DaveLoneRanger ("You're not going crazy! You're going sane in a crazy world!" - The Tick)
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To: grey_whiskers

Cheers? What's the point of a monster size cartoon and screwing up the thread and comments display?


12 posted on 05/17/2006 11:47:02 PM PDT by neverdem (May you be in heaven a half hour before the devil knows that you're dead.)
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To: neverdem

I forgive him... They are wearing Tarheels caps!!!


13 posted on 05/18/2006 4:06:44 AM PDT by cobaltblu
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To: neverdem
I think if we want the whole truth we need to ask the expert: TOM CRUISE

scarcasm

14 posted on 05/18/2006 4:08:26 AM PDT by cobaltblu
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To: neverdem
Correct me if I am wrong, but doesn't Prozac also encourage suicide? If so, is it really a "success"?
15 posted on 05/18/2006 4:26:37 AM PDT by nmh (Intelligent people recognize Intelligent Design (God) !)
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To: neverdem

save


16 posted on 05/18/2006 5:17:39 AM PDT by Eagles6 (Dig deeper, more ammo.)
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To: nmh
Correct me if I am wrong, but doesn't Prozac also encourage suicide? If so, is it really a "success"?

This is sort of an urban myth put forward by the Scientologists. Like all urban myths, it has anectdotal evidence to support it.

Some people on Prozac have committed suicide, true, but often people who are suffering from depression commit suicide. Virtually everyone being treated with Prozac has some form of depression. If Prozac had been shown to have a causal link with suicide, it would be off the market.

Of course, Tom Cruise would disagree with that, but he eats placenta...

17 posted on 05/18/2006 6:21:00 AM PDT by Kenton
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To: nmh
If so, is it really a "success"?

Are you kidding? Have you seen the profit margin?

18 posted on 05/18/2006 6:22:50 AM PDT by Wolfie
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To: neverdem

1: Pak J Pharm Sci. 1999 Jul;12(2):11-6. Related Articles, Links


Inhibition of rat liver tryptophan pyrrolase activity by fluoxetine.

Bano S, Morgan CJ, Badawy AA, Buckland PR, Guffin PM.

Cardiff Community Health Care NHS Trust, Biomedical Research Laboratory, Witchurch Hospital, Cardiff CF4 7XB, UK.

The present study has demonstrated the effectiveness of acute administration of fluoxetine to inhibit rat liver tryptophan pyrrolase activity. The maximum inhibition of basal liver tryptophan pyrrolase activity at 2 h after administration was observed with 1 mg/kg dose for the total enzyme and apoenzyme activities and that significant inhibition of these two activities was evident with a dose of the drug as small as 0.5 mg/kg. Serum free tryptophan concentrations were also increased using 10 mg/kg dose of fluoxetine. In view of the role of tryptophan depletion and thus 5-HT in pathophysiology of depression, it is strongly suggested that the inhibition of liver tryptophan pyrrolase activity may be a major mechanism of antidepressant action.

PMID: 16414828 [PubMed]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed

I wonder if they ever take into account what impact this has on their little mice studies?


19 posted on 05/18/2006 6:28:14 AM PDT by oxcart (Journalism (Sic))
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To: neverdem; All

Who paid for this little smoke and mirrors study? I could never find it in the PDF doc.


20 posted on 05/18/2006 6:47:09 AM PDT by oxcart (Journalism (Sic))
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To: Kenton

http://www.drugawareness.org/Archives/Survivors/survivor_index.html

I'm not a scientologist or believe it is a urban myth. Take a look at the site I provided.


21 posted on 05/18/2006 9:08:53 AM PDT by Irisshlass
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To: All

What concerns me most about prozac is the fact it is showing up in water supplies.

Maybe it is at such a low level that it could never make any difference but it sure seems like something to keep track of.

Personally I am against FDA drugs but I understand that they help some people and those folks should have access to them if they want to.

It scares me to think that massive numbers of people could get their daily dose of prozac without even realizing it.


22 posted on 05/18/2006 9:14:56 AM PDT by BlueStateDepression
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To: nmh

I heard an MD who worked on Prozac and has since regretted that she did so say that suicide and/or violence are attendant side effects.

Virtually every kid who has shot up classrooms was proven to have been taking it or it's cousins.


23 posted on 05/18/2006 9:31:20 AM PDT by Spirited
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To: oxcart
Who paid for this little smoke and mirrors study? I could never find it in the PDF doc.

"Support was provided by the National Alliance for Research on Schizophrenia and Depression, the National Institute of Neurological Disorders and Stroke, The Hartman Foundation, The Ira Hazan Fund, The Seraph Foundation, and The Cody Center for Autism and Developmental Disabilities."

It's at the very end of the text, before the references on the right side of the page. As far as this being a "smoke and mirrors study," from the first paragraph after the abstract:

"However, the cellular basis for the action of SSRIs is not clear. In addition to its effects on neurotransmission, SSRI fluoxetine increases generation of new neurons in the dentate gyrus (DG) of the adult brain (4–9)."

In the sidebar of the pdf browser, click on "Similar articles in PubMed." You'll get at least 2 of those references, e.g. Malberg et al. (2000) J. Neuroscience and Santarelli et al. (2003) Science.

24 posted on 05/18/2006 10:40:58 AM PDT by neverdem (May you be in heaven a half hour before the devil knows that you're dead.)
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To: neverdem

Thanks, any thoughts on post #19?


25 posted on 05/18/2006 11:00:28 AM PDT by oxcart (Journalism (Sic))
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To: Irisshlass

That site lists anecdotal data, which is meaningless in terms of science and true causality. I was on prozac for awhile, but it didn't help. I now take effexor and it is much more effective for me. Do I have some side effects? Yes, but in this case, the problem was much worse than the 'cure'.


26 posted on 05/18/2006 4:28:24 PM PDT by technochick99 ( Firearm of choice: Sig Sauer....)
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To: technochick99

Did you read the site? Anecdotal data?
The ICFDA BOARD
Dr. Ann Blake Tracy

Dr. Ann Blake Tracy, a Ph.D. in Health Sciences with the emphasis on Psychology, is the director of the International Coalition for Drug Awareness. She has specialized for 14 years in adverse reactions to serotonergic medications (such as Prozac, Sarafem, Zoloft, Paxil, Luvox, Celexa, Lexapro, Effexor, Serzone, Anafranil, Fen-Phen, Redux and Meridia) and has testified before the FDA and congressional subcommittee members on Prozac. She has testified since 1992 as an expert witness in Prozac and other SSRI related court cases around the world.

Dr. Candace B. Pert, PhD

Research Professor, Georgetown University Medical Center, Washington, D.C., Former Chief of Brain Biochemistry at NIH for 13 years. She studied the inner workings of the body with an eye towards identifying and locating peptides and receptors

Dr. Julian Whitaker, MD

Dr. Julian Whitaker, founder of the Whitaker Wellness Institute, is one of the country's foremost advocates of healing through diet, exercise, lifestyle changes, and the principles of orthomolecular medicine.

Dr. Lorraine Day, MD

An internationally acclaimed orthopedic trauma surgeon and best selling author was for 15 years on the faculty of the University of California, San Francisco, School of Medicine as Associate Professor and Vice Chairman of the Department of Orthopedics. She was also Chief of Orthopedic Surgery at San Francisco General Hospital and is recognized world-wide as an AIDS expert

Joyce Riley vonKleist, RN, BSN, Captain, USAF inactive Reserve

Has presented at the National Institutes of Health, medical legal conferences such as the American Trail Lawyers Association, was host of her own radio talk show "NurseTalk Radio-The Truth in Health Care", and has guested on over 1500 radio and television shows, including Art Bell, Chuck Harder and Michael Reagan. Served as a Captain in the United States Air Force and flew on C-130 missions in support of Operation Desert Storm. She now serves as spokesperson for the American Gulf War Veterans Association whose purpose is to provide education and information for the Gulf War veterans and their families and to seek treatment for the illnesses that thousands of Gulf War veterans now suffer from.

Dr. Bradford S. Weeks, MD

Bradford S. Weeks, M.D. is a medical doctor whose practice welcomes people all ages suffering with all illnesses. He offers conventional, as well as complementary, medical and psychiatric care. Dr. Weeks' approach is biochemical in nature. That means he works to correct your underlying biochemical imbalances which create your illnesses and pain, rather than to simply offer you various synthetic drugs designed to suppress your symptoms.


Mark M. Miller, ICFDA Web Administrator

Mark and his wife Cheryl lost their 13-year old son to a Zoloft-induced suicide in 1997, Since then, Mark has been serving as the organization's Regional Director in Kansas and developed the ICFDA website to help connect survivors and educate others about the dangerous and often deadly side effects of prescription medications.














27 posted on 05/18/2006 6:02:51 PM PDT by Irisshlass
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To: cobaltblu
ok, I'm just here on the site for the second, but I'm responding to you because you seem to actually have a rational brain regarding this issue.
I'm so sick of people who think they know what they are talking about, even though, like the couch-jumper, they have no scientific basis to back up their idiotic claims.
28 posted on 05/18/2006 7:38:07 PM PDT by Amore (First, let's kill all the lawyers!)
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To: oxcart
Thanks, any thoughts on post #19?

They been working on tryptophan pyrrolase for a long time. It will probably be some time before all the effects of fluoxetine are well understood.

The Specificity of Tryptophan Analogues as Inducers, Substrates, Inhibitors, and Stabilizers of Liver Tryptophan Pyrrolase*

"None of the compounds tested showed the strongly inhibitory action of 5-hydroxytryptophan on the Pseudomonas enzyme (12) or on the liver enzyme (13)."

ENZYME: 1.13.11.11

Check all the names for tryptophan pyrrolase as well as the other entries.

Tryptophan metabolism - Reference pathway

Tryptophan as a Link between Psychopathology and Somatic States

29 posted on 05/18/2006 8:08:40 PM PDT by neverdem (May you be in heaven a half hour before the devil knows that you're dead.)
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To: Irisshlass

Oh lass, I don't know what to make of your reply to me. The data - anecdotal, not statistical. It has nothing to do with scientific proof or causality. So you copied info about their Board. That has nothing to do with my post whatsoever.


30 posted on 05/19/2006 4:52:26 PM PDT by technochick99 ( Firearm of choice: Sig Sauer....)
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To: neverdem

Thanks for the links (((BUMP)))


31 posted on 05/19/2006 7:26:05 PM PDT by oxcart (Journalism (Sic))
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To: airborne

ping


32 posted on 05/19/2006 8:02:51 PM PDT by neverdem (May you be in heaven a half hour before the devil knows that you're dead.)
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