Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Creation of new neurons critical to antidepressant action in mice

08.08.2003


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.

Contact: Jules Asher, mailto:nihmpress@nih.gov

Jules Asher | EurekAlert!
Further information:
http://www.nimh.nih.gov

More articles from Studies and Analyses:

nachricht Amputees can learn to control a robotic arm with their minds
28.11.2017 | University of Chicago Medical Center

nachricht The importance of biodiversity in forests could increase due to climate change
17.11.2017 | Deutsches Zentrum für integrative Biodiversitätsforschung (iDiv) Halle-Jena-Leipzig

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Plasmonic biosensors enable development of new easy-to-use health tests

14.12.2017 | Health and Medicine

New type of smart windows use liquid to switch from clear to reflective

14.12.2017 | Physics and Astronomy

BigH1 -- The key histone for male fertility

14.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>