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Dr. Bob is Robert Hsiung, MD,
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Posted by harlie on August 7, 2003, at 21:19:49
Antidepressants Grow New Brain Cells - U.S. Study
Thu Aug 7, 3:47 PM ET Add Health
By Maggie Fox, Health and Science Correspondent
WASHINGTON (Reuters) - Antidepressants may help stimulate the growth of new brain cells, U.S.-based scientists said on Thursday in releasing research that may lead to the development of better drugs to fight depression.
In Yahoo! Health
--------------------------------------------------------------------------------
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Research on rats shows that two different classes of antidepressants can help brain cells regenerate -- and not in areas normally thought of as being involved in depression.
"This is an important new insight into how antidepressants work," Dr. Thomas Insel, director of the National Institute of Mental Health, said in a statement.
The study fits in with others that suggest depression can shrink the hippocampus, a brain region crucial to learning and memory but only recently found to be involved in depression. Major stress and trauma -- both depression triggers -- can also cause the shrinkage.
"We have known that antidepressants influence the birth of neurons in the hippocampus. Now it appears that this effect may be important for the clinical response," Insel said.
New antidepressants may be developed to target this process directly, said Rene Hen of Columbia University in New York, who led the study.
"The proof in humans is going to come when we extend the work into finding drugs that stimulate neurogenesis. If these drugs have antidepressant effects in humans, this is going to be proof that the process is critical in humans," Hen said in a telephone interview.
"There is a push already in the pharmaceutical industry to find such compounds."
The new study may also help explain why it can take weeks for antidepressants to give patients relief.
"If antidepressants work by stimulating the production of new neurons, there's a built-in delay," said Hen. The stem cells that give rise to new cells need time to divide, to differentiate into neurons, move to their new homes and link up with other neurons.
To make sure that the new brain cells in the hippocampus was the source of the lifted depression, Hen and colleagues at Yale University and in France worked with genetically engineered mice, using X-rays to kill newly growing cells in the hippocampus.
These mice did not respond as they normally would to antidepressants. Mice which were given fluoxetine, an antidepressant sold under the brand-name Prozac by Eli Lilly and Co., and were then given X-rays did not resume grooming as would be expected.
Mice who received no X-rays and were killed after being dosed for 11 or 28 days with fluoxetine showed significant growth of new brain cells.
A drug in a different class, the tricyclic imipramine, also stimulated the growth of neurons, Hen's team reported in Friday's issue of the journal Science.
"Besides finding drugs that target this process, the other basic research challenge for me is to find out what the function of these new neurons is," Hen said.
Experts say that 16 percent of Americans -- more than 30 million people -- will suffer major depression at some point in their lives.
The NIMH says major depression is now the No. 1 leading cause of disability around the world.
Posted by jrbecker on August 8, 2003, at 0:41:05
In reply to Antidepressants Grow New Brain Cells, posted by harlie on August 7, 2003, at 21:19:49
fairly interesting that this is the 2nd study out this month that implicates hippocampal regeneration as integral to the antidepressant effect.
For the first one see...
http://www.dr-bob.org/babble/20030728/msgs/247363.html
This most recent one [below] seems even more conclusive than the first, since the model showed that "blocking the formation of neurons in the hippocampus blocks the behavioral effects of antidepressants in mice."another version of the article from NIH itself
http://www.nih.gov/news/pr/aug2003/nimh-07.htm
go science, go science.
> Antidepressants Grow New Brain Cells - U.S. Study
> Thu Aug 7, 3:47 PM ET Add Health
>
>
> By Maggie Fox, Health and Science Correspondent
>
> WASHINGTON (Reuters) - Antidepressants may help stimulate the growth of new brain cells, U.S.-based scientists said on Thursday in releasing research that may lead to the development of better drugs to fight depression.
>
>
> In Yahoo! Health
>
>
> --------------------------------------------------------------------------------
>
> More from Yahoo! Health:
> • Check your symptoms
> • How is it diagnosed?
> • Learn about treatment
>
>
>
>
>
> Research on rats shows that two different classes of antidepressants can help brain cells regenerate -- and not in areas normally thought of as being involved in depression.
>
>
> "This is an important new insight into how antidepressants work," Dr. Thomas Insel, director of the National Institute of Mental Health, said in a statement.
>
>
> The study fits in with others that suggest depression can shrink the hippocampus, a brain region crucial to learning and memory but only recently found to be involved in depression. Major stress and trauma -- both depression triggers -- can also cause the shrinkage.
>
>
> "We have known that antidepressants influence the birth of neurons in the hippocampus. Now it appears that this effect may be important for the clinical response," Insel said.
>
>
> New antidepressants may be developed to target this process directly, said Rene Hen of Columbia University in New York, who led the study.
>
>
> "The proof in humans is going to come when we extend the work into finding drugs that stimulate neurogenesis. If these drugs have antidepressant effects in humans, this is going to be proof that the process is critical in humans," Hen said in a telephone interview.
>
>
> "There is a push already in the pharmaceutical industry to find such compounds."
>
>
> The new study may also help explain why it can take weeks for antidepressants to give patients relief.
>
>
> "If antidepressants work by stimulating the production of new neurons, there's a built-in delay," said Hen. The stem cells that give rise to new cells need time to divide, to differentiate into neurons, move to their new homes and link up with other neurons.
>
>
> To make sure that the new brain cells in the hippocampus was the source of the lifted depression, Hen and colleagues at Yale University and in France worked with genetically engineered mice, using X-rays to kill newly growing cells in the hippocampus.
>
>
> These mice did not respond as they normally would to antidepressants. Mice which were given fluoxetine, an antidepressant sold under the brand-name Prozac by Eli Lilly and Co., and were then given X-rays did not resume grooming as would be expected.
>
>
> Mice who received no X-rays and were killed after being dosed for 11 or 28 days with fluoxetine showed significant growth of new brain cells.
>
>
> A drug in a different class, the tricyclic imipramine, also stimulated the growth of neurons, Hen's team reported in Friday's issue of the journal Science.
>
>
> "Besides finding drugs that target this process, the other basic research challenge for me is to find out what the function of these new neurons is," Hen said.
>
>
> Experts say that 16 percent of Americans -- more than 30 million people -- will suffer major depression at some point in their lives.
>
>
> The NIMH says major depression is now the No. 1 leading cause of disability around the world.
>
>
>
>
>
>
>
>
>
>
Posted by Ame Sans Vie on August 8, 2003, at 9:13:19
In reply to Antidepressants Grow New Brain Cells, posted by harlie on August 7, 2003, at 21:19:49
Wow, that is so interesting... especially since it may explain why antidepressants have that delayed-onset. Thanks so much for posting this!
Posted by jrbecker on August 8, 2003, at 13:50:12
In reply to 2nd recentstudy involving hippocamp. regeneration , posted by jrbecker on August 8, 2003, at 0:41:05
another interesting article on the study, explains it a little more in detail...
http://www.sciencedaily.com/releases/2003/08/030808081951.htm
Science Daily
Creation Of New Neurons Critical To Antidepressant Action In Mice
Blocking the formation of neurons in the hippocampus blocks the behavioral effects of antidepressants in mice, say researchers funded by the National Institutes of Health (NIH). Their finding lends new credence to the proposed role of such neurogenesis in lifting mood. It also helps to explain why antidepressants typically take a few weeks to work, note Rene Hen, Ph.D., Columbia University, and colleagues, who report on their study in the August 8th Science.
"If antidepressants work by stimulating the production of new neurons, there's a built-in delay," explained Hen, a grantee of NIH's National Institute of Mental Health (NIMH) and National Institute on Drug Abuse (NIDA). "Stem cells must divide, differentiate, migrate and establish connections with post-synaptic targets – a process that takes a few weeks."
"This is an important new insight into how antidepressants work," added NIMH director Thomas Insel, M.D. "We have known that antidepressants influence the birth of neurons in the hippocampus. Now it appears that this effect may be important for the clinical response."
Chronic stress, anxiety and depression have been linked to atrophy or loss of hippocampal neurons. A few years ago, Hen's colleague and co-author Ronald Duman, Ph.D., Yale University, reported that some antidepressants promote hippocampal neurogenesis. But to what effect? To begin to demonstrate a causal relationship between these newly generated cells and relief from depression, researchers would have to find a way to prevent their formation in a behaving animal.
The researchers first showed that mice become less anxious – they begin eating sooner in a novel environment – after four weeks of antidepressant treatment, but not after just 5 days of such treatment. Paralleling the delay in onset of antidepressant efficacy in humans, the chronically-treated mice, but not the briefly-treated ones, showed a 60 percent boost in a telltale marker of neurogenesis in a key area of the hippocampus.
To find out if the observed neurogenesis is involved in antidepressants' mechanism-of -action, Hen and colleagues selectively targeted the hippocampus with x-rays to kill proliferating cells. This reduced neurogenesis by 85 percent. Antidepressants had no effect on anxiety and depression-related behaviors in the irradiated mice. For example, fluoxetine failed to improve grooming behavior, as it normally does, in animals whose behavior had deteriorated following chronic unpredictable stress. Evidence suggested that this could not be attributed to other effects of x-rays
Neurons communicate with each other by secreting messenger chemicals, or neurotransmitters, such as serotonin, which cross the synaptic gulf between cells and bind to receptors on neighboring cell membranes. Medications that enhance such binding of serotonin to its receptors (serotonin selective reuptake inhibitors, or SSRIs) are widely prescribed to treat anxiety and depression, suggesting that these receptors play an important role in regulating emotions.
By knocking out the gene that codes for a key subtype of serotonin receptor (5-HT1A), the researchers created a strain of "knockout" mice that as adults show anxiety-related traits, such as a reluctance to begin eating in a novel environment. While unaffected by chronic treatment with the SSRI fluoxetine, the knockout mice became less anxious after chronic treatment with tricyclic antidepressants, which act via another neurotransmitter, norepinephrine, suggesting an independent molecular pathway.
While chronic fluoxetine treatment doubled the number of new hippocampal neurons in normal mice, it had no effect in the knockout mice. The tricyclic imipramine boosted neurogenesis in both types of mice, indicating that the serotonin 1A receptor is required for neurogenesis induced by fluoxetine, but not imipramine. Chronic treatment with a serotonin 1A-selective drug confirmed that activating the serotonin 1A receptor is sufficient to spur cell proliferation.
Although the new findings strengthen the case that neurogenesis contributes to the effects of antidepressants, Hen cautions that ultimate proof may require a "cleaner" method of suppressing this process, such as transgenic techniques that will more precisely target toxins at the hippocampal circuits involved.
"Our results suggest that strategies aimed at stimulating hippocampal neurogenesis could provide novel avenues for the treatment of anxiety and depressive disorders," suggest the researchers.
Also participating in the study were: Luca Santarelli, Michael Saxe, Cornelius Gross, Stephanie Dulawa, Noelia Weisstaub, James Lee, Columbia University; Alexandre Surget, Catherine Belzung, Universite de Tours, France; Fortunato Battaglia, Ottavio Arancio, New York University.
In addition to NIMH and NIDA, the research was also supported by the National Alliance for Research on Schizophrenia and Depression (NARSAD).NIMH and NIDA are part of the National Institutes of Health (NIH), the Federal Government's primary agency for biomedical and behavioral research. NIH is a component of the U.S. Department of Health and Human Services.
This is the end of the thread.
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