Navigation Links
New strategy for stimulating neurogenesis may lead to drugs to improve cognition and mood

NEW YORK (April 3, 2011) Researchers at Columbia University Medical Center have developed a new way to stimulate neuron production in the adult mouse brain, demonstrating that neurons acquired in the brain's hippocampus during adulthood improve certain cognitive functions.

In recent years, scientists have been exploring whether stimulating neurogenesis (the formation of new neurons) in the adult brain has a beneficial effect on cognition or mood. Until now, studies have relied on interventions, such as exercise and enriched environments, that affect numerous other processes in the brain in addition to increasing adult hippocampal neurogenesis.

The research, led by Ren Hen, PhD, professor of Neuroscience and Pharmacology, in the Departments of Neuroscience and Psychiatry at Columbia University and the New York State Psychiatric Institute, appears in the Advance Online Publication of the journal Nature. Amar Sahay, PhD, a postdoctoral fellow, is the lead author on the study.

After boosting the number of neurons in the hippocampus, an area of the brain involved in memory and mood, the researchers tested the mice in both learning and mood-related tasks and looked for changes in behavior. The researchers found specific effects on learning tasks that involve a process called pattern separation, which is the ability to distinguish between similar places, events and experiences.

"This process is crucial for learning because it enables us to know whether something is familiar or novel," said Dr. Hen. "If it is familiar, you move on to the next bit of information; if it's novel, you want to be able to recognize that it's new and give it meaning. These mice, with just more adult-born neurons, and no other changes in the brain, basically learn better in tasks where they have to discriminate between similar contexts."

Earlier strategies for manipulating neurogenesis, according to the investigators, were broader and less specific. "In addition to stimulating neurogenesis, these earlier methods exerted many other effects on the brain. As a result, you never knew with these older manipulations what's due to neurogenesis, or what's due to the other effects that these manipulations cause, and, indeed, what we find is that when you stimulate just adult neurogenesis, you actually get a subtle effect. Unlike broader manipulations, it does not affect all forms of learning, it's very specific to tasks that require pattern separation," said Dr. Hen.

Pattern separation is not only important for learning; it may also be important for anxiety disorders, including post traumatic stress disorder (PTSD) and panic disorder. People with PTSD, say the researchers, have a more generalized fear response, so that when they are placed in a situation that reminds them of even one aspect of their trauma, they frequently have a full fear response.

"I think a good example of this is someone who has developed PTSD as a result of 9/11. For them, the simple sight of an airplane or high tower may be enough to reawaken the initial traumatic episode and bring back the full aversive memory. Sometimes these generalizations become so pervasive that people basically don't want to leave their home anymore because everything reminds them of the original event," said Dr. Hen.

The normal adaptive response, say the authors of the study, is to separate similar events or experiences. "Even though I may remember 9/11, when I see an airplane over NYC, I am able to recognize that it's a different situation and process it accordingly, while someone in the same situation with PTSD may re-experience the traumatic memory of 9/11 and have a panic attack. So this may be one reason why stimulating neurogenesis to improve pattern separation may contribute to treatment of some of these anxiety disorders," said Dr. Hen.

Enhancing pattern separation, by either the method the Columbia researchers used, or other strategies, may also be useful in treating some of the learning deficits seen in people with normal or pathological aging, such as Alzheimer's disease. In fact, there is already evidence that pattern separation declines during normal aging.

"This paper, as a consequence, may stimulate a whole area of research in humans to try to determine who in the population may have a pattern separation deficit, and whether it is restricted to the emotional domain, or is present even while performing tasks devoid of emotional salience. Once these studies are done in humans, it may be possible to treat these people with specifically targeted drugs or more personalized therapies," said Dr. Hen.

The researchers say that the genetic strategy used to stimulate neurogenesis in their experiments can be mimicked pharmacologically, potentially leading to the development of new drugs to reverse pattern separation deficits. One such class of drugs the investigators are currently testing BAX inhibitors works by blocking cell death.

"These drugs are basically doing the same thing that we did with our genetic manipulationnamely, increasing the survival of the young neurons which normally undergo a process of cell death that eliminates at least half of these neurons. Now instead of dying, the neurons will go on to survive," said Dr. Sahay.

Some BAX inhibitors have been developed for stroke research, where the goal has also been to prevent neurons from dying. The Columbia researchers plan to begin testing the BAX inhibitors in mice shortly. And if they produce cognitive benefits, the testing will be extended to clinical trials to determine if there's also a beneficial effect in humans.

"I think we're getting closer to harnessing neurogenesis to improve cognition and mood in humans. This research may also help explain a bit of a mystery in the field, which we still don't understand, regarding how the hippocampus can be involved with both cognition which is its classic function and in mood and anxiety-related functions. Perhaps the fact that pattern separation affects both the cognitive and mood domains is the beginning of an answer to that paradox," said Dr. Hen.

Contact: Karin Eskenazi
Columbia University Medical Center

Related biology news :

1. Economics and evolution help scientists identify new strategy to control antibiotic resistance
2. Study shows new treatment strategy effective for certain lung cancers
3. H1N1 pandemic points to vaccine strategy for multiple flu strains
4. Canadian marine biodiversity scientists forging strategy for sustainable ocean use
5. New insect birth control strategy zaps cotton pests
6. Frost & Sullivan Honours Fingerprint Cards AB with Product Line Strategy Award
7. A strategy to fix a broken heart
8. UM School of Medicine scientists develop new strategy that may improve cognition
9. Molecular discovery suggests new strategy to fight cancer drug resistance
10. Scientists call for a new strategy for polar ocean observation
11. Flus evolution strategy strikes perfect balance
Post Your Comments:
(Date:11/9/2015)... , Nov. 9, 2015  Synaptics Inc. (NASDAQ: ... today announced broader entry into the automotive market with ... match the pace of consumer electronics human interface innovation. ... are ideal for the automotive industry and will be ... Europe , Japan ...
(Date:11/2/2015)... , Nov. 2, 2015  SRI International has been ... provide preclinical development services to the National Cancer Institute ... will provide scientific expertise, modern testing and support facilities, ... preclinical pharmacology and toxicology studies to evaluate potential cancer ... The PREVENT Cancer Drug Development Program is an ...
(Date:10/29/2015)... Calif. , Oct. 29, 2015  The J. ... new report titled, "DNA Synthesis and Biosecurity: Lessons Learned ... the Department of Health and Human Services guidance for ... in 2010. --> ... it also has the potential to pose unique biosecurity ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... ... November 24, 2015 , ... The Academy of Model ... Group (SIG), MultiGP, also known as Multirotor Grand Prix, to represent the First–Person View ... years. Many AMA members have embraced this type of racing and several new model ...
(Date:11/24/2015)... Israel , Nov. 24, 2015  Tikcro Technologies Ltd. (OTCQB: TIKRF) ... on December 29, 2015 at 11:00 a.m. Israel ... Electra Tower, 98 Yigal Allon Street, 36 th Floor, ... of Eric Paneth and Izhak Tamir to the ... Rami Skaliter as external directors; , approval of an amendment to ...
(Date:11/24/2015)... , ... November 24, 2015 , ... ... the environment are paramount. Insertion points for in-line sensors can represent a weak ... the InTrac 781/784 series of retractable sensor housings , which are designed ...
(Date:11/24/2015)... Nov. 24, 2015 /CNW Telbec/ - ProMetic Life Sciences Inc. ... that Mr. Pierre Laurin , President and Chief Executive ... the upcoming Piper Jaffray 27 th Annual Healthcare Conference ... December 1-2, 2015. st , at 8.50am ... meetings throughout the day. The presentation will be available live ...
Breaking Biology Technology: